Gynecology and Ob-

stetrics

2008 Edition

New Treatment Guidelines

Paul D. Chan, M.D.

Susan M. Johnson, M.D.

Copyright © 2008 Current Clinical Strategies Publishing.

All rights reserved. This book, or any parts thereof, may
not be reproduced or stored in an information retrieval
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reader is advised to consult the package insert and other
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publisher disclaims any liability, loss, injury, or damage
incurred as a consequence, directly or indirectly, of the
use and application of any of the contents of this text.

Surgical Documentation
for Gynecology
Gynecologic History
Identifying Data. Age, gravida (number of pregnancies),
para (number of deliveries).
Chief Compliant. Reason given by patient for seeking
surgical care.
History of Present Illness (HPI). Describe the course of
the patient's illness, including when it began, character
of the symptoms; pain onset (gradual or rapid), charac-
ter of pain (constant, intermittent, cramping, radiating);
other factors associated with pain (urination, eating,
strenuous activities); aggravating or relieving factors.
Other related diseases; past diagnostic testing.
Obstetrical History. Past pregnancies, durations and
outcomes, preterm deliveries, operative deliveries.
Gynecologic History: Last menstrual period, length of
regular cycle.
Past Medical History (PMH). Past medical problems,
previous surgeries, hospitalizations, diabetes, hyperten-
sion, asthma, heart disease.
Medications. Cardiac medications, oral contraceptives,
estrogen.
Allergies. Penicillin, codeine.
Family History. Medical problems in relatives.
Social History. Alcohol, smoking, drug usage, occupa-
tion.
Review of Systems (ROS):
General: Fever, fatigue, night sweats.
HEENT: Headaches, masses, dizziness.
Respiratory: Cough, sputum, dyspnea.
Cardiovascular: Chest pain, extremity edema.
Gastrointestinal: Vomiting, abdominal pain, melena
(black tarry stools), hematochezia (bright red blood
per rectum).
Genitourinary: Dysuria, hematuria, discharge.
Skin: Easy bruising, bleeding tendencies.

Gynecologic Physical Examination

General:
Vital Signs: Temperature, respirations, heart rate, blood
pressure.
Eyes: Pupils equally round and react to light and ac-
commodation (PERRLA); extraocular movements
intact (EOMI).
Neck: Jugular venous distention (JVD), thyromegaly,
masses, lymphadenopathy.
Chest: Equal expansion, rales, breath sounds.
Heart: Regular rate and rhythm (RRR), first and second
heart sounds, murmurs.
Breast: Skin retractions, masses (mobile, fixed), ery-
thema, axillary or supraclavicular node enlargement.
Abdomen: Scars, bowel sounds, masses,
hepatosplenomegaly, guarding, rebound, costoverte-
bral angle tenderness, hernias.
Genitourinary: Urethral discharge, uterus, adnexa,
ovaries, cervix.
Extremities: Cyanosis, clubbing, edema.
Neurological: Mental status, strength, tendon reflexes,
sensory testing.
Laboratory Evaluation: Electrolytes, glucose, liver
function tests, INR/PTT, CBC with differential; X-rays,
ECG (if >35 yrs or cardiovascular disease), urinalysis.
Assessment and Plan: Assign a number to each prob-
lem. Discuss each problem, and describe surgical plans
for each numbered problem, including preoperative
testing, laboratory studies, medications, and antibiotics.

Discharge Summary
Patient's Name:
Chart Number:
Date of Admission:
Date of Discharge:
Admitting Diagnosis:
Discharge Diagnosis:
Name of Attending or Ward Service:
Surgical Procedures:
History and Physical Examination and Laboratory
Data: Describe the course of the disease up to the time
the patient came to the hospital, and describe the physi-
cal exam and laboratory data on admission.
Hospital Course: Describe the course of the patient's
illness while in the hospital, including evaluation, treat-
ment, outcome of treatment, and medications given.
Discharged Condition: Describe improvement or dete-
rioration in condition.
Disposition: Describe the situation to which the patient
will be discharged (home, nursing home).
Discharged Medications: List medications and instruc-
tions.
Discharged Instructions and Follow-up Care: Date of
return for follow-up care at clinic; diet, exercise instruc-
tions.
Problem List: List all active and past problems.
Copies: Send copies to attending physician, clinic, con-
sultants and referring physician.

Surgical Progress Note

Surgical progress notes are written in “SOAP” format.

Surgical Progress Note

Date/Time:
Post-operative Day Number:
Problem List: Antibiotic day number and
hyperalimentation day number if applicable. List
each surgical problem separately (eg, status-post
appendectomy, hypokalemia).
Subjective: Describe how the patient feels in the
patient's own words, and give observations about
the patient. Indicate any new patient complaints,
note the adequacy of pain relief, and passing of
flatus or bowel movements. Type of food the patient
is tolerating (eg, nothing, clear liquids, regular diet).
Objective:
Vital Signs: Maximum temperature (Tmax) over
the past 24 hours. Current temperature, vital
signs.
Intake and Output: Volume of oral and intrave-
nous fluids, volume of urine, stools, drains, and
nasogastric output.
Physical Exam:
General appearance: Alert, ambulating.
Heart: Regular rate and rhythm, no murmurs.
Chest: Clear to auscultation.
Abdomen: Bowel sounds present, soft,
nontender.
Wound Condition: Comment on the wound
condition (eg, clean and dry, good granulation,
serosanguinous drainage). Condition of dress-
ings, purulent drainage, granulation tissue,
erythema; condition of sutures, dehiscence.
Amount and color of drainage
Lab results: White count, hematocrit, and
electrolytes, chest x-ray
Assessment and Plan: Evaluate each numbered
problem separately. Note the patient's general con-
dition (eg, improving), pertinent developments, and
plans (eg, advance diet to regular, chest x-ray). For
each numbered problem, discuss any additional
orders and plans for discharge or transfer.

Procedure Note
A procedure note should be written in the chart when a
procedure is performed. Procedure notes are brief oper-
ative notes.

Procedure Note

Date and time:

Procedure:
Indications:
Patient Consent: Document that the indications,
risks and alternatives to the procedure were ex-
plained to the patient. Note that the patient was
given the opportunity to ask questions and that the
patient consented to the procedure in writing.
Lab tests: Electrolytes, INR, CBC
Anesthesia: Local with 2% lidocaine
Description of Procedure: Briefly describe the
procedure, including sterile prep, anesthesia
method, patient position, devices used, anatomic
location of procedure, and outcome.
Complications and Estimated Blood Loss (EBL):
Disposition: Describe how the patient tolerated the
procedure.
Specimens: Describe any specimens obtained and
laboratory tests which were ordered.

Discharge Note
The discharge note should be written in the patient’s
chart prior to discharge.

Discharge Note

Date/time:
Diagnoses:
Treatment: Briefly describe treatment provided dur-
ing hospitalization, including surgical procedures
and antibiotic therapy.
Studies Performed: Electrocardiograms, CT scans.
Discharge Medications:
Follow-up Arrangements:

Postoperative Check
A postoperative check should be completed on the eve-
ning after surgery. This check is similar to a daily prog-
ress note.
 Example Postoperative Check

Date/time:
Postoperative Check
Subjective: Note any patient complaints, and note
the adequacy of pain relief.
Objective:
General appearance:
Vitals: Maximum temperature in the last 24
hours (Tmax), current temperature, pulse, respira-
tory rate, blood pressure.
Urine Output: If urine output is less than 30 cc
per hour, more fluids should be infused if the
patient is hypovolemic.
Physical Exam:
Chest and lungs:
Abdomen:
Wound Examination: The wound should be
examined for excessive drainage or bleeding,
skin necrosis, condition of drains.
Drainage Volume: Note the volume and charac-
teristics of drainage from Jackson-Pratt drain or
other drains.
Labs: Post-operative hematocrit value and other
labs.
Assessment and Plan: Assess the patient’s overall
condition and status of wound. Comment on abnor-
mal labs, and discuss treatment and discharge
plans.

Total Abdominal Hysterectomy and

Bilateral Salpingo-oophorectomy
Operative Report
Preoperative Diagnosis: 45 year old female, gravida 3
para 3, with menometrorrhagia unresponsive to medical
therapy.
Postoperative Diagnosis: Same as above
Operation: Total abdominal hysterectomy and bilateral
salpingo-oophorectomy
Surgeon:
Assistant:
Anesthesia: General endotracheal
Findings At Surgery: Enlarged 10 x 12 cm uterus with
multiple fibroids. Normal tubes and ovaries bilaterally.
Frozen section revealed benign tissue. All specimens
sent to pathology.
Description of Operative Procedure: After obtaining
informed consent, the patient was taken to the operating
room and placed in the supine position, given general
anesthesia, and prepped and draped in sterile fashion.
A Pfannenstiel incision was made 2 cm above the
symphysis pubis and extended sharply to the rectus
fascia. The fascial incision was bilaterally incised with
curved Mayo scissors, and the rectus sheath was sepa-
rated superiorly and inferiorly by sharp and blunt dissec-
tion. The peritoneum was grasped between two Kelly
clamps, elevated, and incised with a scalpel. The pelvis
was examined with the findings noted above. A Balfour
retractor was placed into the incision, and the bowel was
packed away with moist laparotomy sponges. Two
Kocher clamps were placed on the cornua of the uterus
and used for retraction.
The round ligaments on both sides were clamped,
sutured with #0 Vicryl, and transected. The anterior leaf
of the broad ligament was incised along the bladder
reflection to the midline from both sides, and the bladder
was gently dissected off the lower uterine segment and
cervix with a sponge stick.
The retroperitoneal space was opened and the
ureters were identified bilaterally. The infundibulopelvic
ligaments on both sides were then doubly clamped,
transected, and doubly ligated with #O Vicryl. Excellent
hemostasis was observed. The uterine arteries were
skeletonized bilaterally, clamped with Heaney clamps,
transected, and sutured with #O Vicryl. The uterosacral
ligaments were clamped bilaterally, transected, and
suture ligated in a similar fashion.
The cervix and uterus was amputated, and the vagi-
nal cuff angles were closed with figure-of-eight stitches
of #O Vicryl, and then were transfixed to the ipsilateral
cardinal and uterosacral ligament. The vaginal cuff was
closed with a series of interrupted #O Vicryl, fig-
ure-of-eight sutures. Excellent hemostasis was obtained.
The pelvis was copiously irrigated with warm normal
saline, and all sponges and instruments were removed.
The parietal peritoneum was closed with running #2-O
Vicryl. The fascia was closed with running #O Vicryl. The
skin was closed with stables. Sponge, lap, needle, and
instrument counts were correct times two. The patient
was taken to the recovery room, awake and in stable
condition.
Estimated Blood Loss (EBL): 150 cc
Specimens: Uterus, tubes, and ovaries
Drains: Foley to gravity
Fluids: Urine output - 100 cc of clear urine
Complications: None
Disposition: The patient was taken to the recovery
room in stable condition.

Vaginal Hysterectomy
Hysterectomy is the most common major operation
performed on nonpregnant women. More than one-third
of American women will undergo this procedure. The
surgery may be approached abdominally, vaginally, or
as a laparoscopically assisted vaginal procedure. The
ratio of abdominal to vaginal hysterectomy is approxi-
mately 3:1.

I. Indications for hysterectomy

A. Pelvic relaxation
B. Leiomyomata
C. Pelvic pain (eg, endometriosis)
D. Abnormal uterine bleeding
E. Adnexal mass
F. Cervical intraepithelial neoplasia
G. Endometrial hyperplasia
H. Malignancy
I. Pelvic relaxation is the most common indication
and accounts for 45% of vaginal hysterectomies,
while leiomyomata are the most common indication
(40%) for the abdominal procedure.
II. Route of hysterectomy
A. Vaginal hysterectomy is usually recommended for
women with benign disease confined to the uterus
when the uterine weight is estimated at less than
280 g. It is the preferred approach when pelvic
floor repair is to be corrected concurrently.
B. Contraindications to hysterectomy:
1. Lack of uterine mobility
2. Presence of an adnexal mass requiring removal
3. Contracted bony pelvis
4. Need to explore the upper abdomen
5. Lack of surgical expertise
C. Vaginal hysterectomy is associated with fewer
complications, shorter length of hospitalization,
and lower hospital charges than abdominal hyster-
ectomy.
III. Vaginal hysterectomy operative procedure
A. A prophylactic antibiotic agent (eg, cefazolin
[Ancef] 1g IV) should be given as a single dose 30
minutes prior to the first incision for vaginal or ab-
dominal hysterectomy.
B. The patient should be placed in the dorsal
lithotomy position. When adequate anesthesia is
obtained, a bimanual pelvic examination is per-
formed to assess uterine mobility and descent and
to confirm that no unsuspected adnexal disease is
found. A final decision can then be made whether
to proceed with a vaginal or abdominal approach.
C. The patient is prepared and draped, and bladder
catheter may be inserted. A weighted speculum is
placed into the posterior vagina, a Deaver or right
angle retractor is positioned anterior to the cervix,
and then the anterior and posterior lips of the cer-
vix are grasped with a single- or double-toothed
tenaculum.
D. Traction is placed on the cervix to expose the pos-
terior vaginal mucosa. Using Mayo scissors, the
posterior cul-de-sac is entered sharply, and the
peritoneum identified. A figure-of-eight suture is
then used to attach the peritoneum to the posterior
vaginal mucosa.
E. A Steiner-Anvard weighted speculum is inserted
into the posterior cul-de-sac after this space is
opened. The uterosacral ligaments are clamped,
with the tip of the clamp incorporating the lower
portion of the cardinal ligaments. The clamp is
placed perpendicular to the uterine axis, and the
pedicle cut so that there is 0.5 cm of tissue distal to
the clamp. A transfixion suture is then placed at the
tip of the clamp. Once ligated, the uterosacral liga-
ments are transfixed to the posterior lateral vaginal
mucosa. This suture is held with a hemostat.
F. Downward traction is placed on the cervix to pro-
vide countertraction for the vaginal mucosa and
the anterior vaginal mucosa is incised at the level
of the cervicovaginal junction. The bladder is ad-
vanced upward using an open, moistened gauze
sponge. At this point, the vesicovaginal peritoneal
reflection is usually identified and can be entered
sharply using scissors. A Deaver or Heaney retrac-
tor is placed in the midline to keep the bladder out
of the operative field. Blunt or sharp advancement
of the bladder should precede each clamp place-
ment until the vesicovaginal space is entered.
G. The cardinal ligaments are identified, clamped, cut,
and suture ligated. The bladder is advanced out of
the operative field using blunt dissection technique.
The uterine vessels are clamped to incorporate the
anterior and posterior leaves of the visceral perito-
neum.
H. The anterior peritoneal fold is now visualized, and
the anterior cul-de-sac can be entered. The
peritoneal reflection is grasped with smooth for-
ceps, tented, and opened with scissors with the
tips pointed toward the uterus. A Heaney or
Deaver retractor is placed into this space to protect
the bladder.
I. The uterine fundus is delivered posteriorly by plac-
ing a tenaculum on the uterine fundus in succes-
sive bites. An index finger is used to identify the
utero-ovarian ligament and aid in clamp place-
ment. The remainder of the utero-ovarian liga-
ments are clamped and cut. The pedicles are
double-ligated first with a suture tie and followed by
a suture ligature medial to the first tie.
IV. Discharge instructions
A. The woman is encouraged to resume her normal
daily activities as quickly as is comfortable. Walk-
ing and stair climbing are encouraged; tub baths or
showers are permissible.
B. The patient should avoid lifting over 20 lb of weight
for four to six weeks after surgery to minimize
stress on the healing fascia. Vaginal intercourse is
discouraged during this period. Driving should be
avoided until full mobility returns and narcotic anal-
gesia is no longer required.

Endometrial Sampling and Dilation

and Curettage
The endometrial cavity is frequently evaluated because
of abnormal uterine bleeding, pelvic pain, infertility, or
pregnancy complications. The most common diagnostic
indications for obtaining endometrial tissue include ab-
normal uterine bleeding, postmenopausal bleeding,
endometrial dating, endometrial cells on Papanicolaou
smear, and follow-up of women undergoing medical
therapy for endometrial hyperplasia.

I. Endometrial biopsy
A. The office endometrial biopsy offers a number of
advantages to D&C because it can be done with
minimal to no cervical dilation, anesthesia is not
required, and the cost is approximately one-tenth of
a hospital D&C.
B. Numerous studies have shown that the
endometrium is adequately sampled with these
techniques.
C. Pipelle endometrial sampling device is the most
popular method for sampling the endometrial lining.
The device is constructed of flexible polypropylene
with an outer sheath measuring 3.1 mm in diame-
ter.
D. The device is placed in the uterus through an
undilated cervix. The piston is fully withdrawn to
create suction and, while the device is rotated 360
degrees, the distal port is brought from the fundus
to the internal os to withdraw a sample. The device
is removed and the distal aspect of the instrument
is severed, allowing for the expulsion of the sample
into formalin.
E. The detection rates for endometrial cancer by
Pipelle in postmenopausal and premenopausal
women are 99.6 and 91%, respectively.
F. D&C should be considered when the endometrial
biopsy is nondiagnostic, but a high suspicion of
cancer remains (eg, hyperplasia with atypia, pres-
ence of necrosis, or pyometra).
II. Dilation and curettage
A. Dilation and curettage is performed as either a
diagnostic or therapeutic procedure. Indications for
diagnostic D&C include:
1. A nondiagnostic office biopsy in women who are
at high risk of endometrial carcinoma.
2. Insufficient tissue for analysis on office biopsy.
3. Cervical stenosis prevents the completion of an
office biopsy.
B. Diagnostic D&Cs are usually performed with
hysteroscopy to obtain a visual image of the
 endometrial cavity, exclude focal disease, and pre-
vent missing unsuspected polyps.
C. Examination under anesthesia. After anesthesia
has been administered, the size, shape, and posi-
tion of the uterus are noted, with particular attention
to the axis of the cervix and flexion of the fundus.
The size, shape, and consistency of the adnexa are
determined. The perineum, vagina, and cervix are
then prepared with an aseptic solution and vaginal
retractors are inserted into the vagina.
D. Operative technique. A D&C is performed with the
woman in the dorsal lithotomy position.
1. Endocervical curettage (ECC) is performed
before dilation of the cervix. A Kevorkian-Younge
curette is introduced into the cervical canal up to
the internal os. Curetting of all four quadrants of
the canal should be conducted and the speci-
men placed on a Telfa pad.
2. Sounding and dilation. Traction is applied to
align the axis of the cervix and the uterine canal.
The uterus should be sounded to document the
size and confirm the position. The sound should
be held between the thumb and the index finger
to avoid excessive pressure.
3. Cervical dilation is then performed. The dilator
is grasped in the middle of the instrument with
the thumb and index finger. The cervix is gradu-
ally dilated beginning with the #13 French Pratt
dilator. The dilator should be inserted through
the internal os, without excessively entering the
uterine cavity.
4. Sharp curettage is performed systematically
beginning at the fundus and applying even pres-
sure on the endometrial surface along the entire
length of the uterus to the internal cervical os.
The endometrial tissue is placed on a Telfa pad
placed in the vagina. Moving around the uterus
in a systematic fashion, the entire surface of the
endometrium is sampled. The curettage proce-
dure is completed when the "uterine cry" (gritti-
ness to palpation) is appreciated on all surfaces
of the uterus. Curettage is followed by blind ex-
traction with Randall polyp forceps to improve
the rate of detection of polyps.

General Gynecology
Screening for Cervical Cancer
Cervical cancer screening should be started three years
after the onset of sexual activity, but no later than age
21. The basis of this recommendation is that high grade
cervical intraepithelial lesions (HSIL) are almost entirely
related to acquisition of human papillomavirus (HPV)
infection through genital skin to skin contact and these
lesions usually do not occur until three to five years after
exposure to HPV. HSIL is a precursor to cervical cancer.

I. Screening interval
A. Cervical cancer screening should be started three
years after the onset of sexual activity, but no later
than age 21.
B. The American Cancer Society recommends that
initial cervical screening should be performed an-
nually if conventional cervical cytology smears
(Pap) are used and every two years with liquid-
based cytology tests until age 30. The screening
interval can then be increased to every two to three
years in women with three or more consecutive
normal cytology results who are >30 years old.
C. The American College of Obstetricians and Gyne-
cologists recommends annual screening for
women younger than 30 years of age regardless of
testing method (conventional or liquid-based cytol-
ogy). Women aged 30 and over who have had
three negative smears, no history of CIN II/III, and
are not immunocompromised or DES exposed in
utero may extend the interval between tests to two
to three years. Women aged 30 and over may also
consider the option of a combined cervical cytology
and HPV test. Women who test negative by both
tests should not be screened more frequently than
every three years.
D. Exceptions. Women at increased risk of CIN, such
as those with in utero DES exposure,
immunocompromise, or a history of CIN II/III or
cancer, should continue to be screened at least
annually. More frequent surveillance should also
be considered in women whose smears do not
contain endocervical cells or are partially obscured.
E. Discontinuing screening
1. The United States Preventive Services Task
Force stated screening may stop at age 65 if the
woman has had recent normal smears and is
not at high risk for cervical cancer.
2. The American Cancer Society guideline stated
that women age 70 or older may elect to stop
cervical cancer screening if they have had three
consecutive satisfactory, normal/negative test
results and no abnormal test results within the
prior 10 years.
3. Cervical cancer screening is not recommended
in women who have had total hysterectomies for
benign indications (presence of CIN II or III ex-
cludes benign categorization). Screening of
women with CIN II/III who undergo hysterectomy
may be discontinued after three consecutive
negative results have been obtained. However,
screening should be performed if the woman
acquires risk factors for intraepithelial neoplasia,
such as new sexual partners or
immunosuppression.

Bethesda 2001 Pap Smear Report

Interpretation Result
Negative for intraepithelial lesion or malignancy
Infection (Trichomonas vaginalis, Candida spp., shift in flora
suggestive of bacterial vaginosis, Actinomyces spp., cellu-
lar changes consistent with Herpes simplex virus)
Other Non-neoplastic Findings:
Reactive cellular changes associated with inflammation
(includes typical repair) radiation, intrauterine contra-
ceptive device (IUD)
Glandular cells status post-hysterectomy
Atrophy
Other
Endometrial cells (in a woman >40 years of age)
Epithelial Cell Abnormalities
Squamous Cell
Atypical squamous cells
-of undetermined significance (ASC-US)
-cannot exclude HSIL (ASC-H)
Low-grade squamous intraepithelial lesion (LSIL) en-
compassing: HPV/mild dysplasia/CIN 1
High-grade squamous intraepithelial lesion (HSIL)
encompassing: moderate and severe dysplasia,
CIS/CIN 2 and CIN 3 with features suspicious for
invasion (if invasion is suspected)
Squamous cell carcinoma
Glandular Cell
Atypical
-Endocervical cells (not otherwise specified or
specify in comments)
-Glandular cell (not otherwise specified or specify
in comments)
-Endometrial cells (not otherwise specified or spec-
ify in comments)
-Glandular cells (not otherwise specified or specify
in comments)
Atypical
-Endocervical cells, favor neoplastic
-Glandular cells, favor neoplastic
Endocervical adenocarcinoma in situ
Adenocarcinoma (endocervical, endometrial,
extrauterine, not otherwise specified (not otherwise
specified)
Other Malignant Neoplasms (specify)

Management of the Abnormal Papanicolaou

Smear

Result Action

Specimen adequacy

Satisfactory for evaluation Routine follow-up

Unsatisfactory for evalua- Repeat smear

tion

No endocervical cells Follow-up in one year for

low-risk women with a previ-
ously normal smear; repeat
in 4-6 months for high-risk
women

Atypical cells

Atypical squamous cells of HPV testing with referral to

undetermined significance colposcopy if positive for
(ASC-US) high-risk HPV type; if nega-
tive for high-risk HPV type,
then repeat cytology in 12
months

Special circumstances Postmenopausal women

with atrophic epitheliium
may be treated with topical
estrogen followed by repeat
cervical cytology one week
after completing treatment

ASC-H Immediate referral to

colposcopy

Atypical glandular cells Immediate referral to

(AGS) colposcopy with sampling of
the endocervical canal.
Women over age 35 and
any woman with unex-
plained vaginal bleeding
should also have an
endometrial biopsy

Intraepithelial neoplasia

High grade Immediate referral for

colposcopy

Low grade Immediate referral for

colposcopy, except adoles-
cents and postmenopausal
women

Endometrial cells Endometrial biopsy in se-

lected cases

Other malignant cells Referral to a gynecologic

oncologist

References: See page 208.

Cervical Intraepithelial Neoplasia

Cervical intraepithelial neoplasia (CIN) refers to a
preinvasive pathological intermediate of cervical cancer,
which progresses slowly and can be easily detected and
treated.

I. Nomenclature
A. Histologic definitions of cervical intraepithelial
neoplasia (CIN):
CIN I refers to cellular dysplasia confined to the
basal third of the epithelium
CIN II refers to lesions confined to the basal two-
thirds of the epithelium
CIN III refers to cellular dysplasia encompassing
greater than two-thirds of the epithelial thickness,
including full-thickness lesions
B. Cytologic definitions. Cytologic Pap smears are
classified according to the Bethesda system. In
this system, mild dysplasia/CIN I was combined
with koilocytic or condylomatous atypia to create
the category low-grade squamous intraepithelial
lesion (LSIL or LGSIL). Moderate and severe
dysplasia/CIS/CIN II/CIN III were merged to form
the category of high-grade squamous
intraepithelial lesion (HSIL or HGSIL) because of
similarities in both the cytologic features and prog-
nosis of these groups.
C. Other new terms, such as atypical squamous cells
of undetermined significance (ASCUS) and atypi-
cal glandular cells (AGC), were introduced to ex-
press equivocal findings.
II. Risk factors
A. Sexual activity is a key factor in the etiology of
cervical neoplasia. The incidence of squamous
cell cancer of the cervix in women who have not
had any sexual relationships is almost nonexis-
tent. Sexual risk factors for CIN include sexual
activity at an early age, history of sexually trans-
mitted infections (chlamydia, herpes simplex vi-
rus), multiple sexual partners, or sexual activity
with promiscuous men. The major causal factor is
infection with the human papillomavirus (HPV).
B. Other risk factors include cigarette smoking,
multiparity, and exogenous or endogenous immu-
nodeficiency.
C. Human papillomavirus infection is endemic
among sexually experienced individuals. 80% of
sexually active women will have acquired a genital
HPV infection by age 50. Most HPV infections are
transient, resolving spontaneously in six to 18
months.
D. Diagnosis
1. Cervical cytology. Women are screened for
CIN by cervical cytology (eg, conventional
Papanicolaou smear or liquid based, such as
 ThinPrep or SurePath). Abnormal cytology re-
sults should be further evaluated.
2. Colposcopy is used to evaluate abnormal
cervical cytology. Abnormal areas of the epithe-
lium turn white with dilute acetic acid. Capillar-
ies may be identified within the abnormal epi-
thelium. Capillary thickness and the
intercapillary distances correlate with the sever-
ity of the lesion; high-grade lesions have a
coarser vessel pattern and larger intercapillary
distance. Abnormal areas can be targeted for
biopsy.
III. Management of cervical intraepithelial neopla-
sia
A. Treatment of cervical intraepithelial abnormalities
is undertaken after a histologic abnormality has
been proven by tissue biopsy. Treatment is never
performed based upon a cytologic diagnosis
alone; but is sometimes initiated at the time of
colposcopy/biopsy in women who are at high risk
of loss to follow-up ("see-and-treat" protocols).
B. Atypical squamous cells (ASC, subcategories
ASC-US and ASC-H) is a cytological screening
diagnosis that does not justify treatment because
it is not diagnostic of a cancerous or precancer-
ous lesion. ASC does require further evaluation to
exclude the presence of histologically confirmed
high grade disease, which may require treatment.
C. Low grade lesions: CIN 1
1. Aggressive intervention in these patients is
usually not indicated because a significant
number of these lesions spontaneously regress
and infrequently progress.
2. LSIL regresses to normal in 47%; progression
to a high grade lesion occurs in 21%, and to
cancer in 0.15%.
3. Management. Since spontaneous regression
is observed in most women, expectant man-
agement is generally preferred for the reliable
patient with biopsy-confirmed CIN 1, in whom
the entire lesion and limits of the transformation
zone are completely visualized (ie, satisfactory
colposcopic examination). If treatment is de-
sired, ablative or excisional modalities are ap-
propriate. An excisional procedure is the pre-
ferred diagnostic/therapeutic approach if the
transformation zone is not fully visualizedby
culposcopy.
4. Expectant management. 80 to 85% of
women referred for initial colposcopy because
of LSIL or HPV DNA positive ASC-US have
CIN 1 or less detected on biopsy. 9 to 16% of
these women will have histologically confirmed
CIN 2 or 3 within two years. Expectant man-
agement of women with biopsy confirmed CIN
1 and satisfactory colposcopy consists of re-
peat cytology at 6 and 12 months or HPV test-
ing at 12 months.
a. Colposcopy should be repeated if repeat
cytology shows ASC or greater or HPV DNA
testing is positive for a high risk type.
b. After two negative smears or a negative
HPV DNA test, annual screening may be
resumed.
c. Colposcopy and repeat cytology at 12
months is an acceptable alternative to semi-
annual cytology or annual HPV testing.
5. Ablation or excision
a. Some women may elect to have ablation or
excision of the lesion to relieve their anxiety.
Immediate therapy may also be warranted in
the patient at high risk for loss to follow-up.
b. Endocervical sampling is recommended
before ablation, and excision is recom-
mended for patients with recurrent disease
after ablation. Ablative treatment is unac-
ceptable if colposcopy is not satisfactory. In
such cases, a diagnostic and therapeutic
excisional procedure should be performed.
6. Special circumstances
a. Pregnant and adolescent women. Expec-
tant management of pregnant or adolescent
women with biopsy confirmed CIN 1, even in
the setting of an unsatisfactory colposcopic
examination, is an acceptable alternative to
ablative/excisional therapy because unde-
tected high grade disease is uncommon in
this setting.
b. CIN 1. Expectant management is recom-
mended for the reliable patient in whom the
entire lesion and limits of the transformation
zone are completely visualized. Repeat cy-
tology should be done at 6 and 12 months or
HPV testing at 12 months.
D. High grade lesions: CIN 2/3
1. 43 to 58% of CIN 2 lesions will regress if left
untreated, while 22% progress to CIN 3 and
5% progress to invasive cancer.
2. Management. The entire transformation zone
should be eliminated. Prior to any therapeutic
intervention, an assessment needs to be made
as to whether a patient qualifies for ablative
therapy or if she requires a more invasive
excisional procedure for further diagnostic
work-up.
3. Ablative therapy. Prerequisites for ablative
treatment are:
a. Accurate histologic diagnosis/no discrep-
ancy between cytology/colposcopy/histology
b. No evidence of microinvasion/invasion
c. No evidence of a glandular lesion
(adenocarcinoma in situ or invasive
adenocarcinoma)
d. Satisfactory colposcopy (eg, the transforma-
tion zone is fully visualized)
e. The lesion is limited to the ectocervix and
seen in its entirety
f. There is no evidence of endocervical in-
volvement as determined by
colposcopy/endocervical curettage
4. The most commonly used ablative treatment
techniques are cryotherapy and laser ablation.
5. Excisional therapy. Indications for excisional
therapy are:
a. Suspected microinvasion
b. Unsatisfactory colposcopy (the transforma-
tion zone is not fully visualized)
c. Lesion extending into the endocervical canal

d. Endocervical curettage revealing dysplasia

e. Lack of correlation between the cytology and
colposcopy/biopsies
f. Suspected adenocarcinoma in situ
g. Colposcopist unable to rule out invasive dis-
ease
h. Recurrence after an ablative procedure
6. Excisional treatment can be performed by
cold knife conization, laser conization, or the
loop electrosurgical excision procedure (LEEP).
With suspected microinvasion or ACIS, cold
knife conization is recommended so that mar-
gins can be evaluated without cautery artifact.
7. Special circumstances
a. Pregnancy. High-grade lesions discovered
during pregnancy have a high rate of regres-
sion in the postpartum period. 70% of CIN 3
regress and none progress to invasive carci-
noma. Treatment of CIN 2/3 is not indicated
during pregnancy. The patient should be
monitored with colposcopy (without
endocervical curettage) each trimester.
Colposcopy and cervical cytology should be
performed 6 to 12 weeks postpartum. How-
ever, conization during pregnancy is usually
required in women with suspected invasive
disease.
b. Adolescents. Observation with colposcopy
and cytology at six-month intervals for one
year is acceptable for reliable adolescents
with biopsy-confirmed CIN 2, provided
colposcopy is satisfactory, endocervical cu-
rettage is negative. In this population, the
rate of regression is high and progression to
invasive cancer is extremely small.
(1) Ablation or excision is recommended for
adolescents with CIN 3.
(2) CIN 2/3. Ablative and excisional proce-
dures have equally effective cure rates.
A loop electrosurgical excisional proce-
dure (LEEP) is recommended over an
ablative or other excisional procedures
(cold knife cone). LEEP is an office pro-
cedure with ease of use, providing a
histologic specimen at low cost and mor-
bidity, and high rate of success.
(3) Cold knife conization is recommended
for women with suspected microinvasion,
unsatisfactory colposcopy (eg, the trans-
formation zone is not fully visualized),
lesion extending into the endocervical
canal, and suspected adenocarcinoma in
situ.
E. Therapeutic procedures. The five most common
techniques for treatment of CIN are:
1. Loop electrosurgical excision procedure
(LEEP)
2. Cryotherapy (nitrous oxide or carbon dioxide)
3. Carbon dioxide (CO2) laser ablation
4. Conization (cold knife or laser)
5. These techniques were equally effective, aver-
aging approximately 90% cure.
F. Loop electrosurgical excision procedure. The
loop electrosurgical excision procedure (LEEP)
has become the approach of choice for treating
CIN 2 and 3 because of its ease of use, low cost,
and high rate of success.
G. Cryotherapy refers to the application of a super-
cooled probe (nitrous oxide or carbon dioxide)
directly to the cervical lesion using one or more
cooling and thawing cycles. The probe must be
able to cover the entire lesion and the lesion can-
not extend into the endocervical canal. Anesthesia
is not required.
1. Blanching extend at least 7 to 8 mm beyond
the edge of the cryoprobe to reach the full
depth of the cervical crypts. Typically, the cervix
is frozen for two to three minutes, followed by a
thaw period lasting five minutes. After the cer-
vix has returned to a pink color, an additional
two to three minute freeze application is per-
formed.
2. Conization refers to the excision of a cone
shaped portion of the cervix. The procedure is
usually performed using a scalpel, but laser
conization is also possible. Endocervical curet-
tage can be performed after the conization to
evaluate the remaining endocervical canal.
H. Prognosis and follow-up. Overall, the rate of
recurrent or persistent disease is 5 to 17% despite
therapy with any of the excisional or ablative tech-
niques.
1. Negative margins. There is a high rate of cure
in patients who have their entire lesion excised.
2. Follow-up. Cervical cytology or a combination
of cytology and colposcopy with endocervical
curettage every six months is suggested for
follow-up after treatment of biopsy confirmed
CIN 2/3. Repeat colposcopy is indicated if ASC
or greater is detected. After three results nega-
tive for SIL or malignancy have been obtained,
annual follow-up is acceptable and should be
continued until at least three additional consec-
utive negative results have been documented.
3. Positive margins. In contrast, patients with
positive margins after LEEP or cold knife
conization are at increased risk for residual
disease as determined at subsequent hysterec-
tomy or repeat conization.
4. Follow-up. Women who have positive margins
on the specimens excised by cold knife
conization or LEEP or in the concomitant
endocervical curettage specimen should re-
ceive follow-up with cytology and
colposcopy/biopsy/endocervical curettage (in-
stead of immediate retreatment) if the patient is
likely to be compliant with frequent monitoring.
Alternatively, a repeat excisional procedure can
be offered to women with positive margins who
are averse to the risk of progression. Hysterec-
tomy is an option for women who have com-
pleted childbearing.
5. Negative histopathology. A completely nega-
tive LEEP/cone biopsy performed for high
grade lesions is also of concern, and these
patients should be followed similarly to those
with positive margins, with cytology and
endocervical curettage every six months for at
least the first three visits.
References: See page 208.

Atypical Squamous Cells on Cervi-

cal Cytology
Atypical squamous cells are commonly caused by self-
limited disease, which resolves spontaneously. The risk
of invasive cancer in patients with atypical squamous
cells is low, 0.1 to 0.2%. However, 5 to 17% of patients
with atypical squamous cells and 24 to 94% of those
with ASC-high grade will have precancerous lesions at
biopsy, therefore, further evaluation is necessary to
determine if high-grade dysplasia is present.

I. Evaluation of atypical squamous cells of undeter-

mined significance (ASC-US).
A. Reflex HPV testing with triage of women with high
risk HPV types to colposcopy is the recommended
approach. Reflex testing refers to concurrent col-
lection of cytology and HPV samples with actual
 testing for HPV only if indicated by abnormal cytol-
ogy results.
1. If liquid-based cytology is used, reflex HPV test-
ing can be performed on the same specimen. If
a conventional Papanicolaou (Pap) smear is
obtained, a second specimen is collected for
HPV DNA testing. If high risk subtypes are
found, colposcopy is performed.

Risk of cervical cancer with human papilloma

virus
High-risk (oncogenic or cancer-associated) types
Common types: 16, 18, 31, 33, 35, 39, 45, 51, 52,
56, 58, 59, 68, 69, 82
Low-risk (non-oncogenic) types
Common types: 6, 11, 40, 42, 43, 44, 54, 61, 72, 81

Management of women with combined test

screening
Results of cytol-
ogy/HPV Recommended follow-up

Routine screening in 3
Negative / Negative
years
Repeat combined test in 6
Negative / Positive
to 12 months
Repeat cytology in 12
ASCUS / Negative
months
ASCUS / Positive Colposcopy
Greater than ASCUS
Colposcopy
/ Positive or negative

B. Special circumstances and populations

1. Pregnant women with ASC are managed in
the same way as nonpregnant women, except
endocervical sampling is not performed.
2. Infection or reactive changes. When an in-
fectious organism is identified or suggested,
the patient should be contacted to determine if
she is symptomatic. Antibiotic therapy is indi-
cated for symptomatic infections, as well as
some asymptomatic infections. After treatment
of the infection, women with high risk HPV
types are referred to colposcopy.
3. Atrophic epithelium (a normal finding in
postmenopausal women) is often characterized
by nuclear enlargement, which meets one of
the pathologic criteria for ASC. Administration
of estrogen (eg, 0.3 mg conjugated estrogen
applied as vaginal cream nightly for four weeks
[1/8th of the applicator]) causes atypical atro-
phic, but not dysplastic, epithelium to mature
into normal squamous epithelium. Hormonal
therapy given for vaginal atrophy should be
followed by repeat cervical cytology one week
after completing treatment. If negative, cytology
should be repeated again in six months. If both
tests are negative, the woman can return to
routine screening intervals, but if either test is
positive for ASC-US or greater colposcopy
should be completed.
4. Immunosuppressed women, including all
women who are HIV positive, with ASC-US
should be referred for immediate colposcopy
instead of HPV testing or serial cytology.
5. Adolescents. Initial colposcopy or reflex HPV
testing may be deferred in adolescents be-
cause the risk of invasive cancer is near zero
and the prevalence of transient HPV infection is
very high . Instead, serial cytology should be
completed at six and 12 months or HPV DNA
testing at 12 months with referral to colposcopy
for positive results (ASC or greater, high risk
HPV DNA types).
C. Management after colposcopy/biopsy.
Colposcopy/biopsy of women with ASC-US will
either yield a histologic abnormality (eg, CIN II or
III), which should be treated as appropriate, or
show no abnormal findings. If no abnormal find-
ings are found and HPV testing was not per-
formed or showed a low-risk type, then follow-up
cytological testing in 12 months is recommended.
D. Women who test positive for high risk HPV types,
but have CIN I or less on colposcopy/biopsy re-
quire a repeat cervical cytology at 6 and 12
months, or perform an HPV test at 12 months,
with colposcopy for ASC or higher or a positive
HPV test.
II. Evaluation of atypical squamous cells–cannot
exclude high-grade squamous intraepithelial
lesion (ASC-H)
A. Most women with ASC-H on cytological examina-
tion should be referred for colposcopy and ECC
(ECC is not performed in pregnancy), without HPV
testing. Twenty-four to 94% of these women will
have CIN II or higher. Biopsy proven CIN II or III is
treated, as appropriate.
B. If no lesion or a CIN I lesion is identified, the cytol-
ogy sample, colposcopy, and any biopsy speci-
mens should be reviewed, if possible, to address
any possible cytological-histological discordancy,
with further management dependent upon the
results. If review of cytology confirms ASC-H,
follow-up cytology in six and 12 months or HPV
DNA testing in 12 months is acceptable.
Colposcopy should be repeated for ASC-US or
greater on cytology or a positive test for high risk
HPV DNA.
C. In women age 30 or older with ASC-H, an accept-
able alternative is to perform HPV testing for initial
triaging. If high risk HPV types are present, the
patient is referred for colposcopy.
References: See page 208.

Atypical and Malignant Glandular

Cells on Cervical Cytology
Cervical Pap smear cytology showing atypical glandular
(AGC) or endometrial carcinoma cells indicates the
presence of glandular cells that could originate from the
endocervical or endometrial region. The Bethesda 2001
system classifies AGC into two subcategories:
AGC (specify endocervical, endometrial, or glandu-
lar cells not otherwise specified [NOS])
AGC, favor neoplastic (specify endocervical or
NOS)
Additional categories for glandular cell abnormalities
are:
Endocervical adenocarcinoma in situ (AIS)
Adenocarcinoma

I. Atypical glandular cells

A. A smear with AGC is associated with a
premalignant or malignant lesion of the
endocervix or endometrium in 10 to 40% of cases.
B. Women over age 50 with AGC are at higher risk
of having uterine cancer than younger women (8
and 1%, respectively). Conversely,
premenopausal women with AGC are more likely
to have CIN II/III or AIS than postmenopausal
women.
C. Evaluation. Presence of AGC or AIS on cervical
cytology is a significant marker for neoplasia of
the endometrium, as well as the squamous and
glandular epithelium of the cervix. All women with
atypical glandular cells or AIS should be referred
for colposcopy with directed cervical biopsies and
sampling of the endocervical canal. An
endometrial biopsy should be performed on all
women over age 35 and on younger women with
unexplained or anovulatory bleeding, morbid obe-
sity, oligomenorrhea, or an increased risk of
endometrial cancer.
D. Women with only atypical endometrial cells on
cytology can be initially evaluated with
endometrial biopsy only, rather than colposcopy. If
endometrial sampling is normal, then colposcopy
and endocervical curettage should be performed.
E. Positive findings, such as any grade of CIN on
biopsy, should be managed as appropriate.
F. Negative colposcopy/endocervical curettage.
The management of women with AGC and a neg-
ative initial colposcopy/endocervical sampling
depends upon AGC subclassification.
1. AGC NOS. Women with AGC NOS who have a
normal initial colposcopic evaluation and
endocervical biopsy can be followed with cervi-
cal cytology at four to six month intervals until
four consecutive tests are negative for
intraepithelial lesions or malignancy. They are
then followed with routine surveillance. How-
ever, if any abnormality (ASC or greater) is
noted on follow-up cytology smears, another
colposcopy is required. Women with persistent
AGC NOS (two or more cytology results) are at
especially high risk of significant glandular dis-
ease and need conization if repeat colposcopy
and endometrial biopsy are nondiagnostic.
2. In women with AGC NOS and normal
colposcopic evaluation and biopsies, HPV stud-
ies may be used for further monitoring and, if
negative, repeat cytology and endocervical
sampling can be done in one year rather than
in four visits over two years.
3. AGC favor neoplasia or AIS. A cold-knife
conization is the best procedure for subsequent
evaluation of AGC lesions at high risk of asso-
ciated adenocarcinoma, such as AGC favor
neoplasia or AIS or persistent AGC NOS.
4. If conization and endometrial biopsies are also
negative, the patient should be evaluated for
primary or metastatic disease involving the
fallopian tube, ovary, and other pelvic and ab-
dominal organs with pelvic ultrasound examina-
tion, colonoscopy, and computed tomography
of the abdomen.
II. Endocervical adenocarcinoma
A. Endocervical adenocarcinoma in situ (AIS) and
adenocarcinoma requires evaluation and will
show invasive cancer in a proportion of women
with AIS on cytology. An intermediate category:
atypical endocervical cells, favor neoplastic sug-
gests some features of AIS but without criteria for
a definitive diagnosis.
B. Colposcopy with directed biopsy is required. A
diagnostic excisional procedure is often needed
because colposcopy/biopsy can miss small le-
sions of AIS or adenocarcinoma and lesions high
in the canal.
References: See page 208.

Colposcopy
The colposcope provides an illuminated, magnified view
of the cervix, vagina, and vulva. Malignant and
premalignant epithelium has a characteristic contour,
color, and vascular pattern. The goal of colposcopy is to
identify precancerous and cancerous lesions.

I. Indications for colposcopy

A. Abnormal cytological abnormalities:
1. Persistent atypical squamous cells of undeter-
mined significance (ASCUS) or ASCUS with
positive high-risk HPV subtypes.
2. ASCUS suggestive of high-grade lesion (ASC-
H).
3. Atypical glandular cells (AGC).
4. Low-grade squamous intraepithelial lesion
(LSIL).
5. High-grade squamous intraepithelial lesion
(HSIL).
B. Evaluation of an abnormal appearing cervix, va-
gina, or vulva.
II. Contraindications. Active cervicitis should be treated
before the examination. Biopsies are relatively contra-
indicated in patients on anticoagulations, who have a
known bleeding disorder, or who are pregnant.
III. Procedure. The medical history is obtained, includ-
ing age, gravity, parity, last menstrual period, use
and type of contraception, prior cervical cytology
results, allergies, significant medical history including
HIV status and history of any immunosuppressive
conditions or medications, other medications, prior
cervical procedures, and smoking history. If there is
any possibility of pregnancy, a pregnancy test is
obtained.
A. Repeat cervical cytology. If the patient has not
had cervical cytology in the last six weeks, a re-
peat assessment of cervical cytology is done.
B. Visualization. The cervix and vagina are exam-
ined with a bright light, and then with the
colposcope. Cotton soaked in saline is used to
cleanse the cervix. Pigmented areas and obvious
lesions are noted. The cervix is examined for
areas of erosion, true leukoplakia, pigmented
lesions, or areas of obvious ulceration or
exophytic growth. Three to 5% acetic acid is ap-
plied to the cervix using cotton swabs and the
cervix is reexamined. A green-filter examination
is performed to accentuate abnormal
vasculature. Iodine solution (Lugol's or Schiller's)
is used to improve visualization of abnormal ar-
eas.
C. The clinician first identifies the squamocolumnar
junction or transformation zone (TZ) . The clini-
cian should differentiate between the grey-pink
appearing ectocervix and the pink-red appearing
endocervix. The region where the two cell types
meet, termed the squamocolumnar junction,
defines the "transformation" zone. The ability to
see the transformation zone dictates whether the
 colposcopic exam is adequate (ie, the entire
squamocolumnar junction is visible circumfer-
entially around the os) or unsatisfactory.
D. The upper one-third of the vagina, in particular
the lateral fornices, is also inspected.
E. Biopsies are obtained from the most abnormal
appearing areas. Biopsies should be taken from
inferior to superior to avoid bleeding over the
target sites.
F. Endocervical curettage is performed in patients
with HSIL, AGUS, adenocarcinoma in situ (AIS)
on the endocervical margin following cone bi-
opsy, LSIL but no visible lesion, and those with
an unsatisfactory colposcopic examination. A
long straight curette is used to scrape the four
quadrants of the endocervical canal and an
endocervical brush is employed to remove any
exfoliated tissue. Endocervical curettage in not
performed in pregnant women.
References: See page 208.

Contraception
Approximately 31% of births are unintended; about 22%
were "mistimed," while 9% were "unwanted."

I. Oral contraceptives
A. Combined (estrogen-progestin) oral contracep-
tives are reliable, and they have noncontraceptive
benefits, which include reduction in dysmen-
orrhea, iron deficiency, ovarian cancer,
endometrial cancer.

Combination Oral Contraceptives

Drug Progestin, mg Estrogen

Monophasic combinations

Ortho-Novum 1 Norethindrone (1) Ethinyl estradiol

/35 21, 28 (35)

Ovcon 35 21, 28 Norethindrone Ethinyl estradiol

(0.4) (35)

Brevicon 21, 28 Norethindrone Ethinyl estradiol

(0.5) (35)

Modicon 28 Norethindrone Ethinyl estradiol

(0.5) (35)

Necon 0.5/35E 21, Norethindrone Ethinyl estradiol

28 (0.5) (35)

Nortrel 0.5/35 28 Norethindrone Ethinyl estradiol

(0.5) (35)

Necon 1 /35 21, Norethindrone (1) Ethinyl estradiol

28 (35)

Norinyl 1 /35 21, Norethindrone (1) Ethinyl estradiol

28 (35)

Nortrel 1 /35 21, Norethindrone (1) Ethinyl estradiol

28 (35)

Loestrin 1 /20 21, Norethindrone Ethinyl estradiol

28 acetate (1) (20)

Microgestin 1 /20 Norethindrone Ethinyl estradiol

28 acetate (1) (20)

Loestrin 1.5/30 21, Norethindrone Ethinyl estradiol

28 acetate (1.5) (30)

Microgestin 1.5/30 Norethindrone Ethinyl estradiol

28 acetate (1.5) (30)

Alesse 21, 28 Levonorgestrel Ethinyl estradiol

(0.1) (20)

Aviane 21, 28 Levonorgestrel Ethinyl estradiol

(0.1) (20)

Lessina 28 Levonorgestrel Ethinyl estradiol

(0.1) (20)

Levlite 28 Levonorgestrel Ethinyl estradiol

(0.1) (20)

Necon 1/50 21, 28 Norethindrone (1) Mestranol (50)

Norinyl 1150 21, Norethindrone (1) Mestranol (50)

28

Ortho-Novum 1/50 Norethindrone (1) Mestranol (50)

28

Ovcon 50 28 Norethindrone (1) Ethinyl estradiol

(50)

Cyclessa 28 Desogestrel (0.1) Ethinyl estradiol

(25)

Apri 28 Desogestrel (0.15) Ethinyl estradiol

(30)

Desogen 28 Desogestrel (0.15) Ethinyl estradiol

(30)

Ortho-Cept 21, 28 Desogestrel (0.15) Ethinyl estradiol

(30)

Yasmin 28 Drospirenone (3) Ethinyl estradiol

(30)

Demulen 1 /35 21, Ethynodiol Ethinyl estradiol

28 diacetate (1) (35)

Zovia 1 /35 21, 28 Ethynodiol Ethinyl estradiol

diacetate (1) (35)

Demulen 1/50 21, Ethynodiol Ethinyl estradiol

28 diacetate (1) (50)

Zovia 1 /50 21, 28 Ethynodiol Ethinyl estradiol

diacetate (1) (50)

Levlen 21, 28 Levonorgestrel Ethinyl estradiol

(0.15) (30)

Levora 21, 28 Levonorgestrel Ethinyl estradiol

(0.15) (30)

Nordette 21, 28 Levonorgestrel Ethinyl estradiol

(0.15) (30)

Ortho-Cyclen 21, Norgestimate Ethinyl estradiol

28 (0.25) (35)

Lo/Ovral 21, 28 Norgestrel (0.3) Ethinyl estradiol

(30)

Low-Ogestrel 21, Norgestrel (0.3) Ethinyl estradiol

28 (30)

Ogestrel 28 Norgestrel (0.5) Ethinyl estradiol

(50)

Ovral 21, 28 Norgestrel (0.5) Ethinyl estradiol

(50)

Seasonale Levonorgestrel Ethinyl estradiol

(0.15) (0.03)

Multiphasic Combinations

Kariva 28 Desogestrel (0.15) Ethinyl estradiol

(20, 0, 10)

Mircette 28 Desogestrel (0.15) Ethinyl estradiol

(20, 0, 10)

Tri-Levlen 21, 28 Levonorgestrel Ethinyl estradiol

(0.05, 0.075, (30, 40, 30)
0.125)

Triphasil 21, 28 Levonorgestrel Ethinyl estradiol

(0.05, 0.075, (30, 40, 30)
0.125)

Trivora 28 Levonorgestrel Ethinyl estradiol

(0.05, 0.075, (30, 40, 30)
0.125)

Necon 10/11 21, Norethindrone Ethinyl estradiol

28 (0.5, 1) (35)

Ortho-Novum Norethindrone Ethinyl estradiol

10/11 28 (0.5, 1) (35)

Ortho-Novum Norethindrone Ethinyl estradiol

7/7/7 21, 28 (0.5, 0.75, 1) (35)

Tri-Norinyl 21, 28 Norethindrone Ethinyl estradiol

(0.5, 1, 0.5) (35)

Estrostep 28 Norethindrone Ethinyl estradiol

acetate (1) (20, 30, 35)

Ortho Tri-Cyclen Norgestimate Ethinyl estradiol

21, 28 (0.18, 0.215, 0.25) (35)

B. Pharmacology
1. Ethinyl estradiol is the estrogen in virtually all
OCs.
2. Commonly used progestins include
norethindrone, norethindrone acetate, and
levonorgestrel. Ethynodiol diacetate is a
progestin, which also has significant estrogenic
activity. New progestins have been developed
with less androgenic activity; however, these
agents may be associated with deep vein throm-
bosis.
C. Mechanisms of action
1. The most important mechanism of action is
estrogen-induced inhibition of the midcycle
surge of gonadotropin secretion, so that ovula-
tion does not occur.
2. Another potential mechanism of contraceptive
action is suppression of gonadotropin secretion
during the follicular phase of the cycle, thereby
preventing follicular maturation.
3. Progestin-related mechanisms also may contrib-
ute to the contraceptive effect. These include
rendering the endometrium is less suitable for
implantation and making the cervical mucus less
permeable to penetration by sperm.
D. Contraindications
1. Absolute contraindications to OCs:
a. Previous thromboembolic event or stroke
b. History of an estrogen-dependent tumor
c. Active liver disease
d. Pregnancy
e. Undiagnosed abnormal uterine bleeding
f. Hypertriglyceridemia
g. Women over age 35 years who smoke
heavily (>15 cigarettes per day)
2. Screening requirements. Hormonal contracep-
tion can be safely provided after a careful medi-
cal history and blood pressure measurement.
Pap smears are not required before a prescrip-
tion for OCs.
E. Efficacy. When taken properly, OCs are a very
effective form of contraception. The actual failure
rate is 2 to 3% due primarily to missed pills or fail-
ure to resume therapy after the seven-day pill-free
interval.

Noncontraceptive Benefits of Oral Contraceptive

Pills

Dysmenorrhea Functional ovarian cysts

Mittelschmerz Benign breast cysts
Metrorrhagia Ectopic pregnancy
Premenstrual syndrome Acne
Hirsutism Endometriosis
Ovarian and endometrial
cancer

F. Drug interactions. The metabolism of OCs is

accelerated by phenobarbital, phenytoin and
rifampin. The contraceptive efficacy of an OC is
likely to be decreased in women taking these
drugs. Other antibiotics (with the exception of
rifampin) do not affect the pharmacokinetics of
ethinyl estradiol.
G. Preparations
1. There are two types of oral contraceptive pills:
combination pills that contain both estrogen and
progestin, and the progestin-only pill ("mini-pill").
Progestin-only pills, which are associated with
more breakthrough bleeding than combination
pills, are rarely prescribed except in lactating
women. Combination pills are packaged in 21-
day or 28-day cycles. The last seven pills of a
28-day pack are placebo pills.
2. Monophasic combination pills contain the same
dose of estrogen and progestin in each of the 21
hormonally active pills. Current pills contain on
average 30 to 35 μg. Pills containing less than
50 μg of ethinyl estradiol are "low-dose" pills.
3. 20 µg preparations. Several preparations con-
taining only 20 μg of ethinyl estradiol are now
available (Lo-Estrin 1/20, Mircette, Alesse,
Aviane). These are often used for
perimenopausal women who want contraception
with the lowest estrogen dose possible. These
preparations provide enough estrogen to relieve
 vasomotor flashes. Perimenopausal women
often experience hot flashes and premenstrual
mood disturbances during the seven-day pill-
free interval. Mircette, contains 10 μg of ethinyl
estradiol on five of the seven "placebo" days,
which reduces flashes and mood symptoms.
4. Seasonale is a 91-day oral contraceptive. Tab-
lets containing the active hormones are taken
for 12 weeks (84 days), followed by 1 week (7
days) of placebo tablets. Seasonale contains
levonorgestrel (0.15 mg) and ethinyl estradiol
(0.03 mg). Many women, especially in the first
few cycles, have more spotting between men-
strual periods. Seasonale is as effective and
safe as traditional birth control pills.
5. Yasmin contains 30 mcg of ethinyl estradiol and
drospirenone. Drospirenone has anti-
mineralocorticoid activity. It can help prevent
bloating, weight gain, and hypertension, but it
can increase serum potassium. Yasmin is con-
traindicated in patients at risk for hyperkalemia
due to renal, hepatic, or adrenal disease.
Yasmin should not be combined with other
drugs that can increase potassium, such as
ACE inhibitors, angiotensin receptor blockers,
potassium-sparing diuretics, potassium supple-
ments, NSAIDs, or salt substitutes.
6. Third-generation progestins
a. More selective progestins include
norgestimate, desogestrel, and gestodene.
They have some structural modifications that
lower their androgen activity. Norgestimate
(eg, Ortho-Cyclen or Tri-Cyclen) and
desogestrel (eg, Desogen or Ortho-Cept) are
the least androgenic compounds in this class.
The new progestins are not much less
androgenic than norethindrone.
b. The newer OCs are more effective in reduc-
ing acne and hirsutism in hyperandrogenic
women. They are therefore an option for
women who have difficulty tolerating older
OCs. There is an increased risk of deep ve-
nous thrombosis with the use of these
agents, and they should not be routinely
used.
H. Recommendations
1. Monophasic OCs containing the second genera-
tion progestin, norethindrone (Ovcon 35) are
recommended when starting a patient on OCs
for the first time. This progestin has very low
androgenicity when compared to other second
generation progestins, and also compares favor-
ably to the third generation progestins in
androgenicity.
2. The pill should be started on the first day of the
period to provide the maximum contraceptive
effect in the first cycle. However, most women
start their pill on the first Sunday after the period
starts. Some form of back-up contraception is
needed for the first month if one chooses the
Sunday start, because the full contraceptive
effect might not be provided in the first pill pack.

Factors to Consider in Starting or Switching Oral

Contraceptive Pills

Products that
Objective Action achieve the ob-
jective

To minimize Select a product Alesse, Aviane,

high risk of with a lower dosage Loestrin 1/20,
thrombosis of estrogen. Levlite, Mircette

To minimize Select a product Alesse, Aviane,

nausea, with a lower dosage Levlite, Loestrin
breast ten- of estrogen. 1/20, Mircette
derness or
vascular
headaches

To minimize Select a product Lo/Ovral, Nordette,

spotting or with a higher dos- Ortho-Cept, Ortho-
breakthrough age of estrogen or a Cyclen, Ortho Tri-
bleeding progestin with Cyclen
greater potency.

To minimize Select a product Ovcon 35, Brevicon,

androgenic containing a low- Demulen 1/35,
effects dose norethindrone Modicon
or ethynodiol
diacetate.

To avoid Select a product Ovcon 35, Brevicon,

dyslipidemia containing a low- Demulen 1/35,
dose norethindrone Modicon
or ethynodiol
diacetate.

Instructions on the Use of Oral Contraceptive

Pills

Initiation of use (choose one):

The patient begins taking the pills on the first day of menstrual
bleeding.
The patient begins taking the pills on the first Sunday after
menstrual bleeding begins.
The patient begins taking the pills immediately if she is defi-
nitely not pregnant and has not had unprotected sex since her
last menstrual period.

Missed pill
If it has been less than 24 hours since the last pill was taken,
the patient takes a pill right away and then returns to normal
pill-taking routine.
If it has been 24 hours since the last pill was taken, the patient
takes both the missed pill and the next scheduled pill at the
same time.
If it has been more than 24 hours since the last pill was taken
(ie, two or more missed pills), the patient takes the last pill that
was missed, throws out the other missed pills and takes the
next pill on time. Additional contraception is used for the
remainder of the cycle.

Additional contraceptive method

Use an additional contraceptive method for the first 7 days
after initially starting oral contraceptive pills.
Use an additional contraceptive method for 7 days if more
than 12 hours late in taking an oral contraceptive pill.
Use an additional contraceptive method while taking an inter-
acting drug and for 7 days thereafter.

II. Hormonal contraceptive methods other than oral

contraceptives
A. Contraceptive vaginal ring (NuvaRing) delivers
15 μg ethinyl estradiol and 120 μg of etonogestrel
daily.
1. Advantages of the ring include rapid return to
ovulation after discontinuation, lower doses of
hormones, ease and convenience, and im-
proved cycle control. Benefits, risks, and con-
traindications to use are similar to those with
combined oral contraceptive pills, except for
the convenience of monthly administration.
2. In women who have not used hormonal contra-
ception in the past month, the ring is inserted
on or before day 5 of the menstrual cycle, even
if bleeding is not complete, and an additional
form of contraception should be used for the
following 7 days. New rings should be inserted
at approximately the same time of day the ring
was removed the previous week.
3. If the ring accidentally falls out, it may be rinsed
with cool or warm water and replaced within 3
hours. If it is out of place for more than 3 hours
contraceptive effectiveness decreases, so an
additional form of contraception should be used
until the ring has been inserted for 7 continu-
ous days. If the ring remains in place more than
3 but <4 weeks, it is removed and a new one is
inserted after a 1-week ring-free interval; if the
ring is left in place for >4 weeks, backup con-
traception is recommended until a new ring has
been in place for 7 days.
B. Transdermal contraceptive patch
1. Ortho Evra is a transdermal contraceptive
patch, which is as effective as oral contracep-
tives. Ortho Evra delivers 20 μg of ethinyl
estradiol and 150 μg of norelgestromin daily for
6 to 13 months. Compliance is better with the
patch. The patch is applied at the beginning of
the menstrual cycle. A new patch is applied
each week for 3 weeks; week 4 is patch-free. It
is sold in packages of 3 patches. Effectiveness
is similar to oral contraceptives.
2. Breakthrough bleeding during the first two cy-
cles, dysmenorrhea, and breast discomfort are
more common in women using the patch. A
reaction at the site of application of the patch
occurs in 1.9% of the women. Contraceptive
efficacy may be slightly lower in women weigh-
ing more than 90 kg.
C. Depot medroxyprogesterone acetate (DMPA,
Depo-Provera) is an injectable contraceptive.
Deep intramuscular injection of 150 mg results in
effective contraception for three to four months.
Effectiveness is 99.7%.
D. Women who receive the first injection after the
seventh day of the menstrual cycle should use a
second method of contraception for seven days.
The first injection should be administered within
five days after the onset of menses, in which case
alternative contraception is not necessary.
E. Ovulation is suppressed for at least 14 weeks
after injection of a 150 mg dose of DMPA. There-
fore, injections should repeated every three
months. A pregnancy test must be administered to
women who are more than two weeks late for an
injection.
F. Return of fertility can be delayed for up to 18
months after cessation of DMPA. DMPA is not
ideal for women who may wish to become preg-
nant soon after cessation of contraception.
G. Amenorrhea, irregular bleeding, and weight gain
(typically 1 to 3 kg) are the most common adverse
effects of DMPA. Adverse effects also include
acne, headache, and depression. Fifty% of
women report amenorrhea by one year. Persistent
bleeding may be treated with 50 μg of ethinyl
estradiol for 14 days.
H. Medroxyprogesterone acetate/estradiol
cypionate (MPA/E2C, Lunelle) is a combined (25
mg MPA and 5 mg E2C), injectable contraceptive.

1. Although monthly IM injections are required,

MPA/E2C has several desirable features:
a. It has nearly 100% effectiveness in prevent-
ing pregnancy.
b. Fertility returns within three to four months
after it is discontinued.
c. Irregular bleeding is less common than in
women given MPA alone.
2. Weight gain, hypertension, headache,
mastalgia, or other nonmenstrual complaints
are common.
3. Lunelle should be considered for women who
forget to take their birth control pills or those
who want a discreet method of contraception.
The initial injection should be given during the
first 5 days of the menstrual cycle or within 7
days of stopping oral contraceptives. Lunelle
injections should be given every 28 to 30 days;
33 days at the most.
III. Barrier methods
A. Barrier methods of contraception, such as the
condom, diaphragm, cervical cap, and spermi-
cides, have fewer side effects than hormonal
contraception.
B. The diaphragm and cervical cap require fitting by
a clinician and are only effective when used with
a spermicide. They must be left in the vagina for
six to eight hours after intercourse; the dia-
phragm needs to be removed after this period of
time, while the cervical cap can be left in place
for up to 24 hours. These considerations have
caused them to be less desirable methods of
contraception. A major advantage of barrier con-
traceptives is their efficacy in protecting against
sexually transmitted diseases and HIV infection.
IV. Intrauterine devices
A. The currently available intrauterine devices
(IUDs) are safe and effective methods of contra-
ception:
1. Copper T380 IUD induces a foreign body re-
action in the endometrium. It is effective for 8
to 10 years.
2. Progesterone-releasing IUDs inhibit sperm
survival and implantation. They also decrease
menstrual blood loss and relieve
dysmenorrhea. Paragard is replaced every 10
years. Progestasert IUDs must be replaced
after one year.
3. Levonorgestrel IUD (Mirena) provides effec-
tive contraception for five years.
B. Infection
1. Women who are at low risk for sexually trans-
mitted diseases do not have a higher inci-
dence of pelvic inflammatory disease with use
of an IUD. An IUD should not be inserted in
women at high risk for sexually transmitted
infections, and women should be screened for
the presence of sexually transmitted diseases
before insertion.
2. Contraindications to IUDs:
a. Women at high risk for bacterial
endocarditis (eg, rheumatic heart disease,
prosthetic valves, or a history of
endocarditis).
b. Women at high risk for infections, including
those with AIDS and a history of intrave-
nous drug use.
 c. Women with uterine leiomyomas which al-
ter the size or shape of the uterine cavity.
V. Lactation
A. Women who breast-feed have a delay in resump-
tion of ovulation postpartum. It is probably safest
to resume contraceptive use in the third
postpartum month for those who breast-feed full
time, and in the third postpartum week for those
who do not breast-feed.
B. A nonhormonal contraceptive or progesterone-
containing hormonal contraceptive can be started
at any time; an estrogen-containing oral contra-
ceptive pill should not be started before the third
week postpartum because women are still at
increased risk of thromboembolism prior to this
time. Oral contraceptive pills can decrease
breast milk, while progesterone-containing con-
traceptives may increase breast milk.
VI. Progestin-only agents
A. Progestin-only agents are slightly less effective
than combination oral contraceptives. They have
failure rates of 0.5% compared with the 0.1% rate
with combination oral contraceptives.
B. Progestin-only oral contraceptives (Micronor,
Nor-QD, Ovrette) provide a useful alternative in
women who cannot take estrogen. Progestin-only
contraception is recommended for nursing moth-
ers. Milk production is unaffected by use of
progestin-only agents.
C. If the usual time of ingestion is delayed for more
than three hours, an alternative form of birth con-
trol should be used for the following 48 hours.
Because progestin-only agents are taken contin-
uously, without hormone-free periods, menses
may be irregular, infrequent or absent.
VII. Postcoital contraception
A. Emergency postcoital contraception consists of
administration of drugs within 72 hours to women
who have had unprotected intercourse (including
sexual assault), or to those who have had a fail-
ure of another method of contraception (eg, bro-
ken condom).
B. Preparations
1. Menstrual bleeding typically occurs within
three days after administration of most forms
of hormonal postcoital contraception. A preg-
nancy test should be performed if bleeding
has not occurred within four weeks.
2. Preven Emergency Contraceptive Kit in-
cludes four combination tablets, each contain-
ing 50 μg of ethinyl estradiol and 0.25 mg of
levonorgestrel, and a pregnancy test to rule
out pregnancy before taking the tablets. In-
structions are to take two of the tablets as
soon as possible within 72 hours of coitus, and
the other two tablets twelve hours later.
3. An oral contraceptive such as Ovral (two tab-
lets twelve hours apart) or Lo/Ovral (4 tablets
twelve hours apart) can also be used.
4. Nausea and vomiting are the major side ef-
fects. Meclizine 50 mg, taken one hour before
the first dose, reduces nausea and vomiting
but can cause some sedation.
5. Plan B is a pill pack that contains two 0.75 mg
tablets of levonorgestrel to be taken twelve
hours apart. The cost is comparable to the
Preven kit ($20). This regimen may be more
effective and better tolerated than an
estrogen-progestin regimen.
6. Copper T380 IUD. A copper intrauterine de-
vice (IUD) placed within 120 hours of unpro-
tected intercourse can also be used as a form
of emergency contraception. An advantage of
this method is that it provides continuing con-
traception after the initial event.

Emergency Contraception

1. Consider pretreatment one hour before each oral contra-

ceptive pill dose, using one of the following orally admin-
istered antiemetic agents:
Prochlorperazine (Compazine), 5 to 10 mg
Promethazine (Phenergan), 12.5 to 25 mg
Trimethobenzamide (Tigan), 250 mg
Meclizine (Antivert) 50 mg
2. Administer the first dose of oral contraceptive pill within
72 hours of unprotected coitus, and administer the sec-
ond dose 12 hours after the first dose. Brand name
options for emergency contraception include the follow-
ing:
Preven Kit – two pills per dose (0.5 mg of
levonorgestrel and 100 µg of ethinyl estradiol per
dose)
Plan B – one pill per dose (0.75 mg of levonorgestrel
per dose)
Ovral – two pills per dose (0.5 mg of levonorgestrel
and 100 µg of ethinyl estradiol per dose)
Nordette – four pills per dose (0.6 mg of
levonorgestrel and 120 µg of ethinyl estradiol per
dose)
Triphasil – four pills per dose (0.5 mg of
levonorgestrel and 120 µg of ethinyl estradiol per
dose)

VIII. Sterilization
A. Sterilization is the most common and effective
form of contraception. While tubal ligation and
vasectomy may be reversible, these procedures
should be considered permanent.
B. Essure microinsert sterilization device is a per-
manent, hysteroscopic, tubal sterilization device
which is 99.9% effective. The coil-like device is
inserted in the office under local anesthesia into
the fallopian tubes where it is incorporated by tis-
sue. After placement, women use alternative con-
traception for three months, after which hystero-
salpingography is performed to assure correct
placement. Postoperative discomfort is minimal.
C. Tubal ligation is usually performed as a laparo-
scopic procedure in outpatients or in postpartum
women in the hospital. The techniques used are
unipolar or bipolar coagulation, silicone rubber
band or spring clip application, and partial
salpingectomy.
D. Vasectomy (ligation of the vas deferens) can be
performed in the office under local anesthesia. A
semen analysis should be done three to six
months after the procedure to confirm
azoospermia.
References: See page 208.

Pregnancy Termination
Ninety% of abortions are performed in the first trimester
of pregnancy. About 1.5 million legal abortions are per-
formed each year in the United States. Before 16 weeks
of gestation, legal abortion may be performed in an
office setting. Major anomalies and mid-trimester prema-
ture rupture of membranes are recognized fetal indica-
tions for termination.
I. Menstrual extraction
A. Many women seek abortion services within 1-2
weeks of the missed period. Abortion of these
early pregnancies with a small-bore vacuum can-
nula is called menstrual extraction or minisuction.
The only instruments required are a speculum, a
tenaculum, a Karman cannula, and a modified 50
mL syringe.
B. The extracted tissue is rinsed and examined in a
clear dish of water or saline over a light source to
detect chorionic villi and the gestational sac. This
examination is performed to rule out ectopic preg-
nancy and to decrease the risk of incomplete abor-
tion.
II. First-trimester vacuum curettage
A. Beyond 7 menstrual weeks of gestation, larger
cannulas and vacuum sources are required to
evacuate a pregnancy. Vacuum curettage is the
most common method of abortion. Procedures
performed before 13 menstrual weeks are called
suction or vacuum curettage, whereas similar
procedures carried out after 13 weeks are termed
dilation and evacuation.
B. Technique
1. Uterine size and position should be assessed
during a pelvic examination before the proce-
dure. Ultrasonography is advised if there is a
discrepancy of more than 2 weeks between the
uterine size and menstrual dating.
2. Tests for gonorrhea and chlamydia should be
obtained, and the cervix and vagina should be
prepared with a germicide. Paracervical block is
established with 20 mL of 1% lidocaine injected
deep into the cervix at the 3, 5, 7, and 9 o'clock
positions. The cervix should be grasped with a
single-toothed tenaculum placed vertically with
one branch inside the canal. Uterine depth is
measured with a sound. Dilation then should be
performed with a tapered dilator.
3. A vacuum cannula with a diameter in millime-
ters that is one less than the estimated gesta-
tional age should be used to evacuate the cav-
ity. After the tissue is removed, there should be
a quick check with a sharp curette, followed by
a brief reintroduction of the vacuum cannula.
The aspirated tissue should be examined as
described previously.
4. Antibiotics are used prophylactically .
Doxycycline is the best agent because of a
broad spectrum of antimicrobial effect. D-nega-
tive patients should receive D (Rho[D]) immune
globulin.
C. Complications
1. The most common postabortal complications
are pain, bleeding, and low-grade fever. Most
cases are caused by retained gestational tissue
or a clot in the uterine cavity. These symptoms
are best managed by a repeat uterine evacua-
tion, performed under local anesthesia
2. Cervical shock. Vasovagal syncope produced
by stimulation of the cervical canal can be seen
after paracervical block. Brief tonic-clonic activ-
ity rarely may be observed and is often con-
fused with seizure. The routine use of atropine
with paracervical anesthesia or the use of con-
scious sedation prevents cervical shock.
3. Perforation
a. The risk of perforation is less than 1 in every
1,000 first-trimester abortions. It increases
with gestational age and is greater for
parous women than for nulliparous women.
Perforation is best evaluated by laparoscopy
to determine the extent of the injury.
b. Perforations at the junction of the cervix and
lower uterine segment can lacerate the as-
cending branch of the uterine artery within
the broad ligament, giving rise to severe
pain, a broad ligament hematoma, and
intraabdominal bleeding. Management re-
quires laparotomy, ligation of the severed
vessels, and repair of the uterine injury.
4. Hemorrhage
a. Excessive bleeding may indicate uterine
atony, a low-lying implantation, a pregnancy
of more advanced gestational age than the
first trimester, or perforation. Management
requires rapid reassessment of gestational
age by examination of the fetal parts already
extracted and gentle exploration of the uter-
ine cavity with a curette and forceps. Intrave-
nous oxytocin should be administered, and
the abortion should be completed. The
uterus then should be massaged to ensure
contraction.
b. When these measures fail, the patient
should be hospitalized and should receive
intravenous fluids and have her blood cross-
matched. Persistent postabortal bleeding
strongly suggests retained tissue or clot
(hematometra) or trauma, and laparoscopy
and repeat vacuum curettage is indicated.
5. Hematometra. Lower abdominal pain of in-
creasing intensity in the first 30 minutes sug-
gests hematometra. If there is no fever or
bleeding is brisk, and on examination the
uterus is large, globular, and tense,
hematometra is likely. The treatment is immedi-
ate reevacuation.
6. Ectopic pregnancy, incomplete abortion, and
failed abortion
a. Early detection of ectopic pregnancy, incom-
plete abortion, or failed abortion is possible
with examination of the specimen immedi-
ately after the abortion. The patient may
have an ectopic pregnancy if no chorionic
villi are found. To detect an incomplete abor-
tion that might result in continued preg-
nancy, the actual gestational sac must be
identified.
b. Determination of the b-hCG level and frozen
section of the aspirated tissue and vaginal
ultrasonography may be useful. If the b-hCG
level is >1,500-2,000 mIU, chorionic villi are
not identified on frozen section, or retained
tissue is identified by ultrasonography, im-
mediate laparoscopy should be considered.
Other patients may be followed closely with
serial b-hCG assays until the problem is
resolved. With later (>13 weeks) gestations,
all of the fetal parts must be identified by the
surgeon to prevent incomplete abortion.
c. Heavy bleeding or fever after abortion sug-
gests retained tissue. If the postabortal
uterus is larger than 12-week size, preoper-
ative ultrasonography should be performed
to determine the amount of remaining tis-
sue. When fever is present, high-dose intra-
venous antibiotic therapy with two or three
 agents should be initiated, and curettage
should be performed shortly thereafter.
III. Mifepristone (RU-486) for medical abortion in
the first trimester
A. The FDA has approved mifepristone for termina-
tion of early pregnancy as follows: Eligible women
are those whose last menstrual period began
within the last 49 days. The patient takes 600 mg
of mifepristone (three 200 mg tablets) by mouth on
day 1, then 400 μg misoprostol orally two days
later.
B. A follow-up visit is scheduled on day 14 to confirm
that the pregnancy has been terminated with mea-
surement of b-hCG or ultrasonography.
IV. Second-trimester abortion. Most abortions are
performed before 13 menstrual weeks. Later abor-
tions are generally performed because of fetal
defects, maternal illness, or maternal age.
A. Dilation and evacuation
1. Transcervical dilation and evacuation of the
uterus (D&E) is the method most commonly
used for mid-trimester abortions before 21
menstrual weeks. In the one-stage technique,
forcible dilation is performed slowly and care-
fully to sufficient diameter to allow insertion of
large, strong ovum forceps for evacuation. The
better approach is a two-stage procedure in
which multiple Laminaria are used to achieve
gradual dilatation over several hours before
extraction. Uterine evacuation is accomplished
with long, heavy forceps, using the vacuum
cannula to rupture the fetal membranes, drain
amniotic fluid, and ensure complete evacuation.
2. Preoperative ultrasonography is necessary for
all cases 14 weeks and beyond. Intraoperative
real-time ultrasonography helps to locate fetal
parts within the uterus.
3. Dilation and evacuation becomes progressively
more difficult as gestational age advances, and
instillation techniques are often used after 21
weeks. Dilation and evacuation can be offered
in the late mid-trimester, but two sets of
Laminaria tents for a total of 36-48 hours is
recommended. After multistage Laminaria
treatment, urea is injected into the amniotic
sac. Extraction is then accomplished after labor
begins and after fetal maceration has occurred.
References: See page 208.

Ectopic Pregnancy
Ectopic pregnancy occurs when the conceptus implants
outside the endometrial cavity. Ectopic pregnancy typi-
cally occurs six to eight weeks after the last normal
menstrual period. Normal pregnancy discomforts (eg,
breast tenderness, frequent urination, nausea) are often
present.

I. Clinical evaluation
A. History. The classic symptoms of ectopic preg-
nancy are: Abdominal pain, amenorrhea, and
vaginal bleeding
B. Ectopic pregnancy should be suspected in any
women of reproductive age with these symptoms.
These symptoms are not diagnostic of ectopic
pregnancy; threatened abortion presents with the
same symptoms and is far more common.
C. Blood leaking out of the fallopian tube may irritate
the diaphragm and cause shoulder pain, whereas
blood pooling in the cul-de-sac may cause an urge
to defecate. Lightheadedness or shock suggests
tubal rupture and severe intraabdominal hemor-
rhage.
D. Physical examination. Vital signs may reveal
orthostatic changes and low grade fever. Adnexal
tenderness, cervical motion tenderness, abdomi-
nal tenderness, an adnexal mass, and mild uterine
enlargement may also be present.

Risk Factors for Ectopic Pregnancy

Greatest Risk
Previous ectopic pregnancy
Previous tubal surgery or sterilization
Diethylstilbestrol exposure in utero
Documented tubal pathology (scarring)
Use of intrauterine contraceptive device

Greater Risk
Previous genital infections (eg, PID)
Infertility (In vitro fertilization)
Multiple sexual partners

Lesser Risk
Previous pelvic or abdominal surgery
Cigarette smoking
Vaginal douching
Age of 1st intercourse <18 years

Presenting Signs and Symptoms of Ectopic

Pregnancy

Symptom Percentage

Abdominal pain 80-100%

Amenorrhea 75-95%
Vaginal bleeding 50-80%
Dizziness, fainting 20-35%
Urge to defecate 5-15%
Pregnancy symp- 10-25%
toms 5-10%
Passage of tissue

Adnexal tenderness 75-90%

Abdominal tender- 80-95%

ness

Adnexal mass 50%

Uterine enlargement 20-30%

Orthostatic changes 10-15%

Fever 5-10%

II. Diagnosis
A. Differential diagnosis of abdominal pain in
women: Urinary tract infection, kidney stones,
diverticulitis, appendicitis, ovarian neoplasms,
endometriosis, endometritis, leiomyomas, pelvic
inflammatory disease, and pregnancy-related
conditions.
B. Pregnancy testing is important in
premenopausal women who present with abdom-
inal pain or vaginal bleeding.
C. Amenorrhea and abdominal pain, with or without
vaginal bleeding, are common symptoms of
threatened abortion, ruptured or torsed corpus
luteum cyst, and degenerating uterine
leiomyoma.
D. Diagnostic tests. Transvaginal ultrasound ex-
amination (TVS) is the most useful test for deter-
mining the location of a pregnancy. Transvaginal
ultrasound is used to detect the presence (or
absence) of a gestational sac within or outside of
the uterus.
E. Diagnosis of intrauterine pregnancy. Ultra-
sound is most useful for identifying an
intrauterine gestation. The earliest sonographic
sign of an intrauterine pregnancy is the presence
of a true gestational sac, which has double
echogenic rings surrounding the sac. TVS will
show the gestational sac at 4.5 to 5 weeks of
gestation, the yolk sac appears at 5 to 6 weeks
and remains until 10 weeks, and an embryo with
cardiac activity is first detected at 5.5 to 6 weeks.
1. Concomitant intrauterine and extrauterine
gestation is very rare (ie, heterotopic preg-
nancy occurs in 1/30,000 spontaneous con-
ceptions). Therefore, the identification of an
intrauterine pregnancy effectively excludes the
possibility of an ectopic pregnancy.
F. Diagnosis of extrauterine pregnancy. Visual-
ization of an extrauterine gestational sac contain-
ing a yolk sac or embryo is diagnostic of ectopic
pregnancy, but is detected in only a small propor-
tion of cases.
1. A complex adnexal mass in the presence of a
positive pregnancy test and empty uterus is
highly suggestive of an extrauterine gestation
and is the most common sonographic abnor-
mality.
2. Other nonspecific findings consistent with
ectopic pregnancy include a fluid filled adnexal
mass surrounded by an echogenic ring (bagel
sign) and free fluid in the peritoneal cavity/cul-
de-sac.
G. Human chorionic gonadotropin (hCG) can be
detected in serum and urine as early as eight
days after the LH surge, if pregnancy has oc-
curred. The hCG concentration in a normal
intrauterine pregnancy rises in a curvilinear fash-
ion until about 41 days of gestation, after which it
rises more slowly to 10 weeks, and then declines
until reaching a plateau in the second and third
trimesters. There is a wide range in the normal
hCG level.
H. Discriminatory zone is based upon the correla-
tion between visibility of the gestational sac and
the hCG concentration. It is defined as the serum
hCG level above which a gestational sac should
be visualized by ultrasound if an intrauterine
pregnancy is present. In most institutions, this
serum hCG level is 1500 or 2000 IU/L with
transvaginal ultrasound.
1. The absence of an intrauterine gestational sac
at hCG concentrations above the discrimina-
tory zone strongly suggests an ectopic or
nonviable intrauterine pregnancy, but is
nondiagnostic with hCG values below the dis-
criminatory zone. A negative ultrasound exam-
ination at hCG levels below the discriminatory
zone is consistent with an early viable
intrauterine pregnancy or an ectopic preg-
nancy or nonviable intrauterine pregnancy.
Such cases are termed "pregnancy of un-
known location" and 8 to 40% are ultimately
diagnosed as ectopic pregnancies.
I. Diagnostic evaluation. The evaluation of a
pregnant woman with suspected ectopic gesta-
tion begins with TVS and quantitative hCG level.
TVS alone is diagnostic if a yolk sac, embryo, or
embryonic cardiac activity is demonstrable.
1. HCG above the discriminatory zone. Visual-
ization of an intrauterine pregnancy almost
always excludes the presence of an ectopic
pregnancy.
2. If TVS does not reveal an intrauterine preg-
nancy and shows a complex adnexal mass,
an extrauterine pregnancy is almost certain.
Embryonic cardiac activity or a gestational sac
with a definite yolk sac or embryo at an
extrauterine location is diagnostic of an
ectopic gestation. Treatment of ectopic preg-
nancy should be initiated.
3. If no complex adnexal mass can be visual-
ized, the diagnosis of ectopic pregnancy is
less certain. Furthermore, a serum hCG
>1500 IU/L without visualization of intrauterine
or extrauterine pathology may represent a
multiple gestation. The next step in this setting
is to repeat the TVS examination and hCG
concentration two days later. If an intrauterine
pregnancy is still not observed on TVS, then
the pregnancy is abnormal.
a. An ectopic pregnancy can be diagnosed if
the serum hCG concentration is increasing
or plateaued. Treatment can be instituted.
b. Falling hCG concentration is most consis-
tent with a failed pregnancy, such as ar-
rested pregnancy, blighted ovum, tubal
abortion or spontaneously resolving ectopic
pregnancy. Weekly hCG concentrations
should be monitored until the result is nega-
tive for pregnancy.
c. HCG below the discriminatory zone. TVS
is not sensitive for determining the location
of the pregnancy when the hCG level is
below the discriminatory zone. A serum
hCG concentration less than 1500 IU/L
should be followed by repetition of hCG in
three days to follow the rate of rise. HCG
concentrations usually double every 1.4 to
two days until six to seven weeks of gesta-
tion in viable intrauterine pregnancies (and
in some ectopic gestations).
4. A normally rising hCG concentration should be
evaluated with TVS when the hCG reaches
the discriminatory zone. At that time, an
intrauterine pregnancy or an ectopic preg-
nancy can be diagnosed.
5. If the hCG concentration does not double over
72 hours, then the pregnancy is abnormal (an
ectopic gestation or intrauterine pregnancy
that is destined to abort). A normal intrauterine
pregnancy is not present.
6. If an adnexal mass is visualized on TVS, then
medical or surgical treatment is administered
for a presumed ectopic pregnancy. If an
adnexal mass is not visualized, methotrexate
may be given or a curettage may be done to
determine the type of nonviable pregnancy.
7. A falling hCG concentration is most consistent
with a failed pregnancy (eg, arrested preg-
nancy, blighted ovum, tubal abortion, sponta-
 neously resolving ectopic pregnancy). Weekly
hCG concentrations should be monitored until
the result is negative for pregnancy.
III. Management of ectopic pregnancy
A. Specific indications for surgery: (1) ruptured
ectopic pregnancy, especially in a
hemodynamically unstable woman, (2) contrain-
dications to medical therapy, (3) lack of timely
access to a medical institution for management
of tubal rupture, and (4) failed medical therapy.
B. Medical and surgical therapy are equally suc-
cessful in women who are hemodynamically sta-
ble and have an hCG concentration less than
5000 mIU/mL, a small tubal diameter, and no
fetal cardiac activity. There is a reduction in the
efficacy of medical therapy in the setting of a high
serum hCG concentration, large tubal size, and
fetal cardiac activity.
C. Relative contraindications to methotrexate
1. High hCG concentration. Women with a high
baseline hCG >5000 mIU/mL are more likely
to require multiple courses of medical therapy
or experience treatment failure; conservative
laparoscopic surgery is recommended for
these patients.
2. Large ectopic size >3.5 cm.
3. Fetal cardiac activity is a relative contraindica-
tion to medical treatment.
D. Contraindications. Women who are
hemodynamically unstable, not likely to be com-
pliant with post-therapeutic monitoring (or unwill-
ing to accept a blood transfusion), and who do
not have timely access to a medical institution
should be treated surgically.
1. Specific contraindications to methotrexate
include breastfeeding women, immunodefi-
ciency, active pulmonary disease, peptic ulcer
disease, hypersensitivity to the drug, and sig-
nificant hepatic, renal, or hematologic disease.

Criteria for Receiving Methotrexate

Absolute indications
Hemodynamically stable without active bleeding or signs of
hemoperitoneum
Nonlaparoscopic diagnosis
Patient desires future fertility
General anesthesia poses a significant risk
Patient is able to return for follow-up care
Patient has no contraindications to methotrexate

Relative indications
Unruptured mass <3.5 cm at its greatest dimension
No fetal cardiac motion detected
Patients whose bet-hCG level does not exceed 5,000
mlU/mL

Contraindications to Methotrexate Therapy

Absolute contraindications
Breast feeding
Overt or laboratory evidence of immunodeficiency
Alcoholism, alcoholic liver disease, or other chronic liver
disease
Preexisting blood dyscrasias, such as bone marrow
hypoplasia, leukopenia, thrombocytopenia, or significant
anemia
Known sensitivity to methotrexate
Active pulmonary disease
Peptic ulcer disease
Hepatic, renal, or hematologic dysfunction
Relative contraindications
Gestational sac >3.5 cm
Embryonic cardiac motion

E. Methotrexate administration
1. The overall rate of resolution of ectopic preg-
nancy is about 90%.
2. Single dose protocol. The most practical ap-
proach to therapy is administration of a single
intramuscular dose of methotrexate (50 mg
per square meter of body surface area).
3. Rh(D) immune globulin should be adminis-
tered if the woman is Rh(D)-negative and the
blood group of her male partner is Rh(D)-posi-
tive or unknown.
4. Measurement of serum beta-hCG concentra-
tion and ultrasound examination are per-
formed weekly. A second dose of
methotrexate is given if the serum beta-hCG
concentration on Day 7 has not declined by at
least 25% from the Day 0 level. A second
dose of MTX is required in 15 to 20% of
women.
5. The beta-hCG concentration usually declines
to less than 15 mIU/mL by 35 days post-injec-
tion, but may take as long as 109 days.
Weekly assays should be obtained until a level
less than 10 to 15 mIU/mL is reached.
F. Side effects, monitoring, and complications. Ad-
verse reactions to methotrexate are usually mild
and self-limiting. The most common are
stomatitis and conjunctivitis. Rare side effects
include gastritis, enteritis, dermatitis, pneumoni-
tis, alopecia, elevated liver enzymes, and bone
marrow suppression.
G. It is common to observe an increase in beta-hCG
levels in the three days following therapy be-
cause of continued hCG production by
syncytiotrophoblast.
IV. Operative management can be accomplished by
either laparoscopy or laparotomy. Linear
salpingostomy or segmental resection is the proce-
dure of choice if the fallopian tube is to be retained.
Salpingectomy is the procedure of choice if the tube
requires removal.
References: See page 208.

Acute Pelvic Pain

I. Clinical evaluation
A. Assessment of acute pelvic pain should determine
the patient’s age, obstetrical history, menstrual
history, characteristics of pain onset, duration, and
palliative or aggravating factors.
B. Associated symptoms may include urinary or
gastrointestinal symptoms, fever, abnormal bleed-
ing, or vaginal discharge.
C. Past medical history. Contraceptive history, surgi-
cal history, gynecologic history, history of pelvic
inflammatory disease, ectopic pregnancy, sexually
transmitted diseases should be determined. Cur-
rent sexual activity and practices should be as-
sessed.
D. Method of contraception
1. Sexual abstinence in the months preceding the
onset of pain lessons the likelihood of
pregnancy-related etiologies.
2. The risk of acute PID is reduced by 50% in pa-
tients taking oral contraceptives or using a bar-
rier method of contraception. Patients taking oral
contraceptives are at decreased risk for an
ectopic pregnancy or ovarian cysts.
E. Risk factors for acute pelvic inflammatory dis-
ease. Age between 15-25 years, sexual partner
with symptoms of urethritis, prior history of PID.
II. Physical examination
A. Fever, abdominal or pelvic tenderness, and
peritoneal signs should be sought.
B. Vaginal discharge, cervical erythema and dis-
charge, cervical and uterine motion tenderness, or
adnexal masses or tenderness should be noted.
III. Laboratory tests
A. Pregnancy testing will identify pregnancy-related
causes of pelvic pain. Serum beta-HCG becomes
positive 7 days after conception. A negative test
virtually excludes ectopic pregnancy.
B. Complete blood count. Leukocytosis suggest an
inflammatory process; however, a normal white
blood count occurs in 56% of patients with PID and
37% of patients with appendicitis.
C. Urinalysis. The finding of pyuria suggests urinary
tract infection. Pyuria can also occur with an in-
flamed appendix or from contamination of the urine
by vaginal discharge.
D. Testing for Neisseria gonorrhoeae and
Chlamydia trachomatis are necessary if PID is a
possibility.
E. Pelvic ultrasonography is of value in excluding
the diagnosis of an ectopic pregnancy by demon-
strating an intrauterine gestation. Sonography may
reveal acute PID, torsion of the adnexa, or acute
appendicitis.
F. Diagnostic laparoscopy is indicated when acute
pelvic pain has an unclear diagnosis despite com-
prehensive evaluation.
III. Differential diagnosis of acute pelvic pain
A. Pregnancy-related causes. Ectopic pregnancy,
spontaneous, threatened or incomplete abortion,
intrauterine pregnancy with corpus luteum bleed-
ing.
B. Gynecologic disorders. PID, endometriosis, ovar-
ian cyst hemorrhage or rupture, adnexal torsion,
Mittelschmerz, uterine leiomyoma torsion, primary
dysmenorrhea, tumor.
C. Nonreproductive tract causes
1. Gastrointestinal. Appendicitis, inflammatory
bowel disease, mesenteric adenitis, irritable
bowel syndrome, diverticulitis.
2. Urinary tract. Urinary tract infection, renal calcu-
lus.
IV. Approach to acute pelvic pain with a positive
pregnancy test
A. In a female patient of reproductive age, presenting
with acute pelvic pain, the first distinction is whether
the pain is pregnancy-related or non-pregnancy-
related on the basis of a serum pregnancy test.
B. In the patient with acute pelvic pain associated with
pregnancy, the next step is localization of the tissue
responsible for the hCG production. Transvaginal
ultrasound should be performed to identify an
intrauterine gestation. Ectopic pregnancy is charac-
terized by a noncystic adnexal mass and fluid in the
cul-de-sac.
V. Approach to acute pelvic pain in non-pregnant
patients with a negative HCG
A. Acute PID is the leading diagnostic consideration
in patients with acute pelvic pain unrelated to preg-
nancy. The pain is usually bilateral, but may be
unilateral in 10%. Cervical motion tenderness,
fever, and cervical discharge are common findings.
B. Acute appendicitis should be considered in all
patients presenting with acute pelvic pain and a
negative pregnancy test. Appendicitis is character-
ized by leukocytosis and a history of a few hours of
periumbilical pain followed by migration of the pain
to the right lower quadrant. Neutrophilia occurs in
75%. A slight fever exceeding 37.3EC, nausea,
vomiting, anorexia, and rebound tenderness may
be present.
C. Torsion of the adnexa usually causes unilateral
pain, but pain can be bilateral in 25%. Intense,
progressive pain combined with a tense, tender
adnexal mass is characteristic. There is often a
history of repetitive, transitory pain. Pelvic
sonography often confirms the diagnosis. Laparo-
scopic diagnosis and surgical intervention are indi-
cated.
D. Ruptured or hemorrhagic corpus luteal cyst
usually causes bilateral pain, but it can cause uni-
lateral tenderness in 35%. Ultrasound aids in diag-
nosis.
E. Endometriosis usually causes chronic or recurrent
pain, but it can occasionally cause acute pelvic
pain. There usually is a history of dysmenorrhea
and deep dyspareunia. Pelvic exam reveals fixed
uterine retrodisplacement and tender uterosacral
and cul-de-sac nodularity. Laparoscopy confirms
the diagnosis.
References: See page 208.

Chronic Pelvic Pain

Chronic pelvic pain (CPP) is menstrual or nonmenstrual
pain of at least six months' duration, located below the
umbilicus and severe enough to cause functional disabil-
ity or require treatment. Gynecologic conditions account
for 90% of cases of CPP. Gastrointestinal diseases,
such as irritable bowel syndrome, are the next most
common category.

I. Differential diagnosis
A. Endometriosis is the most common etiology of
CPP in populations with a low prevalence of sexu-
ally transmitted infections. Endometriosis is found
in up to 70% of patients with CPP.
B. Chronic pelvic inflammatory disease (PID) is
one of the most common gynecologic conditions
causing CPP in practices with a high prevalence
of sexually transmitted diseases.
C. Mental-health issues. Somatization disorder,
drug seeking behavior and narcotic dependency,
physical and sexual abuse, and depression are
commonly diagnosed in women with CPP.
D. Fibromyalgia. Women with fibromyalgia some-
times present with CPP. Two criteria must be
present for diagnosing fibromyalgia: The patient
reports pain in all four quadrants of the body, and
detection of at least 11 separate areas (eg, knees,
shoulders, elbows, neck) that are tender to physi-
cal pressure.
E. Irritable bowel syndrome (IBS) is a gastrointesti-
nal syndrome characterized by chronic abdominal
pain and altered bowel habits in the absence of
any organic cause.
F. Interstitial cystitis is characterized by urinary
urgency, bladder discomfort, and a sense of inad-
equate emptying of the bladder. Dyspareunia is
often present. Cystoscopy is diagnostic.
 Some Causes of Chronic Pelvic Pain by System
Gynecologic Systemic diseases

Endometriosis Fibromyalgia
Adenomyosis Depression
Leiomyomata Somatization
Adhesions Substance abuse
Ovarian cyst/mass
Pelvic inflammatory disease
Endosalpingiosis
Cervical stenosis
Pelvic relaxation

Urologic Gastrointestinal

Interstitial cystitis Irritable bowel

Urethral disorders Diverticulitis
Inflammatory bowel disease
Constipation
Hernia

II. History
A. Characteristics of the pain should be noted,
including location, intensity quality, duration, tem-
poral pattern, precipitating factors (eg, exertion,
sexual activity, menses, pregnancy), relationship
to urination and defecation, and radiation.
B. Hormonal versus nonhormonal
1. Pelvic pain associated with severe
dysmenorrhea and/or pain at the time of ovula-
tion is likely due to endometriosis or
adenomyosis. Women with endometriosis re-
port premenstrual spotting, dyspareunia,
dyschezia, poor relief of symptoms with
nonsteroidal anti-inflammatory drugs, progres-
sively worsening symptoms, inability to attend
work or school during menses, and the pres-
ence of pelvic pain unrelated to menses more
often than women with primary dysmenorrhea.
2. Nonhormonally responsive diseases should be
considered for pain that is not related to men-
ses, including chronic pelvic inflammatory dis-
ease, adhesions/inflammation from previous
pelvic surgery, irritable bowel syndrome, diver-
ticulitis, fibromyalgia, and interstitial cystitis.
III. Physical examination
A. Surgical scars, hernias, and masses should be
sought. Pelvic examination should include an
evaluation for physical findings consistent with
endometriosis, adenomyosis, or leiomyomata.
Tender areas should be identified.
B. Physical findings characteristic of
endometriosis are uterosacral ligament abnor-
malities (eg, nodularity or thickening, focal tender-
ness), lateral displacement of the cervix caused
by endometriosis, and cervical stenosis.
C. Adnexal enlargement may be palpable if an
endometrioma is present.
D. Nongynecologic physical findings that are ob-
served more frequently among women with
endometriosis are red hair color, scoliosis, and
dysplastic nevi.
E. Adenomyosis and leiomyomata. Women with
adenomyosis can have a slightly enlarged, globu-
lar, tender uterus. Uterine myomas are character-
ized by enlarged, mobile uterus with an irregular
contour.
F. Chronic pelvic inflammatory disease is charac-
terized by uterine tenderness or cervical motion
tenderness. Adhesions resulting from a surgical
procedure can cause pain, especially with move-
ment of viscera. An adnexal mass suggests an
ovarian neoplasm. Adnexa tenderness suggests
an inflammatory process. In women with uterine
prolapse, the cervix/uterus may be observed pro-
truding from the vagina.

Physical Examination in Women with Chronic

Pelvic Pain

Pelvic Examination

Tenderness present?
Nodularity present?
Pelvic mass?

Abdominal examination

Abdominal distension?
Tenderness present?

Straight leg raising test

Does leg rasing induce pain in the right or left lower

quadrant?

IV. Laboratory and imaging tests for women with

CPP include:
A. Complete blood count with differential and eryth-
rocyte sedimentation rate
B. Pregnancy test.
C. Urinalysis.
D. Pelvic ultrasound.
E. Additional evaluations include testing for
chlamydia and gonorrhea infection and CA-125
(if ascites present).
F. Pelvic ultrasound is highly sensitive for detecting
pelvic masses, including both ovarian cysts and
uterine leiomyomas.
V. Pharmacologic treatment
A. High probability of endometriosis
1. Nonsteroidal anti-inflammatory medications
should be prescribed at doses in the upper
end of the dose range (eg, ibuprofen 800 mg
orally every six hours). If the first NSAID tried
is not effective, another should be given.
2. Oral contraceptive pills (OCPs) prescribed as
monthly cycles.
3. OCPs prescribed as "long cycles," with three
to four months of continuous dosing of the
active pill followed by one week off the pill are
effective in women who fail cyclic therapy.
4. OCPs and NSAIDS can be prescribed individ-
ually or in combination.

Summary of Recommendations for Treatment of

Chronic Pelvic Pain American College of Obste-
tricians and Gynecologists

Intervention Indication

Combined oral contracep- Primary dysmenorrhea

tive pills

GnRH agonists Endometriosis, irritable

bowel syndrome (may be
given empirically in women
with symptoms consistent
with endometriosis)

Nonsteroidal anti-inflamma- Dysmenorrhea, moderate

tory drugs pain

Progestins (daily, high dose) Endometriosis, pelvic con-

gestion syndrome

Laparoscopic abla- Stage I-III endometriosis

tion/resection of
endometriosis

Presacral neurectomy Centrally located

dysmenorrhea

Uterine nerve ablation Centrally located

dysmenorrhea

Adjunctive psychotherapy CPP

B. Second-line agents consist of one of the fol-

lowing:
1. Continuous progestin treatment.
Medroxyprogesterone acetate (50 mg orally
daily), norethindrone acetate (eg, Aygestin 5
mg orally daily), norgestrel (eg, Ovrette 0.075
mg orally daily), or norethindrone (eg, Micronor,
Nor-QD 0.35 mg orally daily) for a two-month
trial.
2. Danazol 200 to 400 mg/day in two divided
doses initially, may be increased to 800 mg/day
in two divided doses to achieve amenorrhea.
Therapy may be continued up to nine months.
3. Empiric use of a gonadotropin-releasing hor-
mone (GnRH) agonist analogue (eg, leuprolide
[3.75 mg intramuscularly every four weeks] or
nafarelin [200 µg intranasally twice daily]) for 2
months. An add-back regimen should be con-
sidered.
4. Surgical intervention, such as laparoscopy or
cystoscopy, can be considered if medical inter-
ventions are not successful or as an initial pro-
cedure to exclude neoplasia or an
endometrioma.
C. Low probability of endometriosis. Women in
whom a particular disease process is suspected,
such as adenomyosis, uterine leiomyomata, irrita-
ble bowel syndrome, interstitial cystitis, diverticuli-
tis, or fibromyalgia should undergo further diag-
nostic testing and disease-specific treatment.
1. Women with suspected pelvic inflammatory
disease infection can be treated with
doxycycline 100 mg orally twice daily for 14
days.
2. NSAIDs can be prescribed at doses in the up-
per end of the dose range (eg, ibuprofen 800
mg orally every six hours).
3. Antidepressants, opioids, anticonvulsants, and
psychotherapy are used for treatment of
chronic pain.
VI. Surgical approach
A. Many causes of CPP, such as endometriosis,
chronic pelvic inflammatory disease, and of a
pelvic mass, require a surgical procedure to deter-
mine a definitive diagnosis. In addition to provid-
ing a diagnosis of endometriosis, surgical excision
of the endometriosis implants can be performed
during the laparoscopy.
B. Hysterectomy is effective in relieving chronic
pelvic pain in some women, who have completed
child bearing.
C. Presacral neurectomy refers to interruption of
the sympathetic innervation of the uterus. The
procedure can be performed via laparoscopy or
laparotomy. PSN is most effective for relieving
midline pelvic pain.
References: See page 208.

Endometriosis
Endometriosis is characterized by the presence of
endometrial tissue on the ovaries, fallopian tubes or
other abnormal sites, causing pain or infertility. Women
are usually 25 to 29 years old at the time of diagnosis.
Approximately 24% of women who complain of pelvic
pain are subsequently found to have endometriosis. The
overall prevalence of endometriosis is estimated to be 5
to 10%.
I. Clinical evaluation
A. Endometriosis should be considered in any woman
of reproductive age who has pelvic pain. The most
common symptoms are dysmenorrhea,
dyspareunia, and low back pain that worsens dur-
ing menses. Rectal pain and painful defecation
may also occur. Other causes of secondary
dysmenorrhea and chronic pelvic pain (eg, upper
genital tract infections, adenomyosis, adhesions)
may produce similar symptoms.

Differential Diagnosis of Endometriosis

Generalized pelvic pain Dyspareunia

Pelvic inflammatory Musculoskeletal causes (pel-
disease vic relaxation, levator
Endometritis spasm)
Pelvic adhesions Gastrointestinal tract (consti-
Neoplasms, benign or pation, irritable bowel syn-
malignant drome)
Ovarian torsion Urinary tract (urethral syn-
Sexual or physical drome, interstitial cystitis)
abuse Infection
Nongynecologic Pelvic vascular congestion
causes Diminished lubrication or
Dysmenorrhea vaginal expansion because
Primary of insufficient arousal
Secondary Infertility
(adenomyosis, Male factor
myomas, infection, Tubal disease (infection)
cervical stenosis) Anovulation
Cervical factors (mucus,
sperm antibodies, stenosis)
Luteal phase deficiency

B. Infertility may be the presenting complaint for

endometriosis. Infertile patients often have no
painful symptoms.
C. Physical examination. The physician should
palpate for a fixed, retroverted uterus, adnexal
and uterine tenderness, pelvic masses or
nodularity along the uterosacral ligaments. A
rectovaginal examination should identify
uterosacral, cul-de-sac or septal nodules. Most
women with endometriosis have normal pelvic
findings.
II. Treatment
A. Confirmatory laparoscopy is usually required be-
fore treatment is instituted. In women with few
symptoms, an empiric trial of oral contraceptives
or progestins may be warranted to assess pain
relief.
B. Medical treatment
1. Initial therapy also should include a
nonsteroidal anti-inflammatory drug.
a. Naproxen (Naprosyn) 500 mg followed by
250 mg PO tid-qid prn [250, 375,500 mg].
b. Naproxen sodium (Aleve) 200 mg PO tid
prn.
c. Naproxen sodium (Anaprox) 550 mg, fol-
lowed by 275 mg PO tid-qid prn.
d. Ibuprofen (Motrin) 800 mg, then 400 mg PO
q4-6h prn.
e. Mefenamic acid (Ponstel) 500 mg PO fol-
lowed by 250 mg q6h prn.
2. Progestational agents. Progestins are similar
to combination OCPs in their effects on FSH,
LH and endometrial tissue. They may be asso-
ciated with more bothersome adverse effects
than OCPs. Progestins are effective in reducing
the symptoms of endometriosis. Oral progestin
regimens may include once-daily administration
of medroxyprogesterone at the lowest effective
dosage (5 to 20 mg). Depot
medroxyprogesterone may be given intramus-
cularly every two weeks for two months at 100
mg per dose and then once a month for four
months at 200 mg per dose.
3. Oral contraceptive pills (OCPs) suppress LH
and FSH and prevent ovulation. Combination
OCPs alleviate symptoms in about three quar-
ters of patients. Oral contraceptives can be
taken continuously (with no placebos) or cycli-
cally, with a week of placebo pills between cy-
cles. The OCPs can be discontinued after six
months or continued indefinitely.
4. Danazol (Danocrine) has been highly effective
in relieving the symptoms of endometriosis, but
adverse effects may preclude its use. Adverse
effects include headache, flushing, sweating
and atrophic vaginitis. Androgenic side effects
include acne, edema, hirsutism, deepening of
the voice and weight gain. The initial dosage
should be 800 mg per day, given in two divided
oral doses. The overall response rate is 84 to
92%.

Medical Treatment of Endometriosis

Adverse ef-
Drug Dosage fects

Danazol 800 mg per day in 2 di- Estrogen defi-

(Danocrine) vided doses ciency,
androgenic
side effects

Oral contra- 1 pill per day (continuous Headache,

ceptives or cyclic) nausea, hyper-
tension

Medroxyprog 5 to 20 mg orally per day Same as with

esterone other oral
(Provera) progestins

Medroxyprog 100 mg IM every 2 weeks Weight gain,

esterone sus- for 2 months; then 200 mg depression,
pension IM every month for 4 irregular men-
(Depo- months or 150 mg IM ev- ses or
Provera) ery 3 months amenorrhea

Norethindron 5 mg per day orally for 2 Same as with

e (Aygestin) weeks; then increase by other oral
2.5 mg per day every 2 progestins
weeks up to 15 mg per
day

Leuprolide 3.75 mg IM every month Decrease in

(Lupron) for 6 months bone density,
estrogen defi-
ciency

Goserelin 3.6 mg SC (in upper ab- Estrogen defi-

(Zoladex) dominal wall) every 28 ciency
days

Nafarelin 400 mg per day: 1 spray Estrogen defi-

(Synarel) in 1 nostril in a.m.; 1 spray ciency, bone
in other nostril in p.m.; density
start treatment on day 2 to changes, nasal
4 of menstrual cycle irritation

C. GnRH agonists. These agents (eg, leuprolide

[Lupron], goserelin [Zoladex]) inhibit the secretion
of gonadotropin. GnRH agonists are contraindi-
cated in pregnancy and have hypoestrogenic side
effects. They produce a mild degree of bone loss.
Because of concerns about osteopenia, “add-
back” therapy with low-dose estrogen has been
recommended. The dosage of leuprolide is a sin-
gle monthly 3.75-mg depot injection given intra-
muscularly. Goserelin, in a dosage of 3.6 mg, is
administered subcutaneously every 28 days. A
nasal spray (nafarelin [Synarel]) may be used twice
daily. The response rate is similar to that with
danazol; about 90% of patients experience pain
relief.
D. Surgical treatment
1. Surgical treatment is the preferred approach to
infertile patients with advanced endometriosis.
Laparoscopic ablation of endometriosis lesions
may result in a 13% increase in the probability of
pregnancy.
2. Definitive surgery, which includes hysterectomy
and oophorectomy, is reserved for women with
intractable pain who no longer desire preg-
nancy.
References: See page 208.

Primary Amenorrhea
Amenorrhea (absence of menses) results from dysfunc-
tion of the hypothalamus, pituitary, ovaries, uterus, or
vagina. It is often classified as either primary (absence
of menarche by age 16) or secondary (absence of men-
ses for more than three cycle intervals or six months in
women who were previously menstruating).

I. Etiology
A. Primary amenorrhea is usually the result of a
genetic or anatomic abnormality. Common etiolo-
gies of primary amenorrhea:
1. Chromosomal abnormalities causing gonadal
dysgenesis: 45%
2. Physiologic delay of puberty: 20%
3. Müllerian agenesis: 15%
4. Transverse vaginal septum or imperforate hy-
men: 5%
5. Absent production of gonadotropin-releasing
hormone (GnRH) by the hypothalamus: 5%
6. Anorexia nervosa: 2%
7. Hypopituitarism: 2%

Causes of Primary and Secondary Amenorrhea

Abnormality Causes

Pregnancy

Anatomic abnormalities

Congenital abnormality Isolated defect

in Mullerian development
Testicular feminization syn-
drome
5-Alpha-reductase defi-
ciency
Vanishing testes syndrome
Defect in testis determining
factor

Congenital defect of uro- Agenesis of lower vagina

genital sinus develop- Imperforate hymen
ment

Acquired ablation or Asherman’s syndrome

scarring of the Tuberculosis
endometrium

Disorders of
hypothalamic-pituitary
ovarian axis
Hypothalamic dysfunc-
tion
Pituitary dysfunction
Ovarian dysfunction

Causes of Amenorrhea due to Abnormalities in

the Hypothalamic-Pituitary-Ovarian Axis

Abnormality Causes

Hypothalamic dys- Functional hypothalamic

function amenorrhea
Weight loss, eating disorders
Exercise
Stress
Severe or prolonged illness
Congenital gonadotropin-releasing
hormone deficiency
Inflammatory or infiltrative diseases
Brain tumors - eg,
craniopharyngioma
Pituitary stalk dissection or compres-
sion
Cranial irradiation
Brain injury - trauma, hemorrhage,
hydrocephalus
Other syndromes - Prader-Willi,
Laurence-Moon-Biedl

Pituitary dysfunc- Hyperprolactinemia

tion Other pituitary tumors- acromegaly,
corticotroph adenomas (Cushing's
disease)
Other tumors - meningioma,
germinoma, glioma
Empty sella syndrome
Pituitary infarct or apoplexy

Ovarian dysfunc- Ovarian failure (menopause)

tion Spontaneous
Premature (before age 40 years)
Surgical

Other Hyperthyroidism
Hypothyroidism
Diabetes mellitus
Exogenous androgen use

II. Diagnostic evaluation of primary amenorrhea

A. Step I: Evaluate clinical history:
1. Signs of puberty may include a growth spurt,
absence of axillary and pubic hair, or apocrine
sweat glands, or absence of breast develop-
ment. Lack of pubertal development suggests
ovarian or pituitary failure or a chromosomal
abnormality.
2. Family history of delayed or absent puberty
suggests a familial disorder.
3. Short stature may indicate Turner syndrome or
hypothalamic-pituitary disease.
4. Poor health may be a manifestation of
hypothalamic-pituitary disease. Symptoms of
other hypothalamic-pituitary disease include
headaches, visual field defects, fatigue, or
polyuria and polydipsia.
5. Virilization suggests polycystic ovary syn-
drome, an androgen-secreting ovarian or adre-
nal tumor, or the presence of Y chromosome
material.
6. Recent stress, change in weight, diet, or exer-
cise habits; or illness may suggest hypotha-
lamic amenorrhea.
7. Heroin and methadone can alter hypothalamic
gonadotropin secretion.
8. Galactorrhea is suggestive of excess prolactin.
Some drugs cause amenorrhea by increasing
serum prolactin concentrations, including
metoclopramide and antipsychotic drugs.
B. Step II: Physical examination
1. An evaluation of pubertal development should
include current height, weight, and arm span
(normal arm span for adults is within 5 cm of
height) and an evaluation of the growth chart.
2. Breast development should be assessed by
Tanner staging.
3. The genital examination should evaluate
clitoral size, pubertal hair development, intact-
ness of the hymen, depth of the vagina, and
presence of a cervix, uterus, and ovaries. If the
vagina can not be penetrated with a finger,
rectal examination may allow evaluation of the
internal organs. Pelvic ultrasound is also useful
to determine the presence or absence of
müllerian structures.
4. The skin should be examined for hirsutism,
acne, striae, increased pigmentation, and
vitiligo.
5. Classic physical features of Turner syndrome
include low hair line, web neck, shield chest,
and widely spaced nipples.
C. Step III: Basic laboratory testing
1. If a normal vagina or uterus are not obvi-
ously present on physical examination, pelvic
ultrasonography should be performed to con-
firm the presence or absence of ovaries,
uterus, and cervix. Ultrasonography can be
 useful to exclude vaginal or cervical outlet ob-
struction in patients with cyclic pain.
a. Uterus absent
(1) If the uterus is absent, evaluation should
include a karyotype and serum testos-
terone. These tests should distinguish
abnormal müllerian development (46,
XX karyotype with normal female serum
testosterone concentrations) from an-
drogen insensitivity syndrome (46, XY
karyotype and normal male serum tes-
tosterone concentrations).
(2) Patients with 5-alpha reductase defi-
ciency also have a 46, XY karyotype and
normal male serum testosterone con-
centrations but, in contrast to the andro-
gen insensitivity syndrome which is as-
sociated with a female phenotype, these
patients undergo striking virilization at
the time of puberty (secondary sexual
hair, muscle mass, and deepening of
the voice).
2. Uterus present. For patients with a normal
vagina and uterus and no evidence of an im-
perforate hymen, vaginal septum, or congenital
absence of the vagina. Measurement of serum
beta human chorionic gonadotropin to exclude
pregnancy and of serum FSH, prolactin, and
TSH.
a. A high serum FSH concentration is indica-
tive of primary ovarian failure. A karyotype is
then required and may demonstrate com-
plete or partial deletion of the X chromo-
some (Turner syndrome) or the presence of
Y chromatin. The presence of a Y chromo-
some is associated with a higher risk of go-
nadal tumors and makes gonadectomy
mandatory.
b. A low or normal serum FSH concentration
suggests functional hypothalamic
amenorrhea, congenital GnRH deficiency,
or other disorders of the hypothalamic-pitu-
itary axis. Cranial MR imaging is indicated in
most cases of hypogonadotropic
hypogonadism to evaluate hypothalamic or
pituitary disease. Cranial MRI is recom-
mended for all women with primary
hypogonadotropic hypogonadism, visual
field defects, or headaches.
c. Serum prolactin and thyrotropin (TSH)
should be measured, especially if
galactorrhea is present.
d. If there are signs or symptoms of hirsutism,
serum testosterone and
dehydroepiandrosterone sulfate (DHEA-S)
should be measured to assess for an
androgen-secreting tumor.
e. If hypertension is present, blood tests
should be drawn for evaluate for CYP17
deficiency. The characteristic findings are
elevations in serum progesterone (>3
ng/mL) and deoxycorticosterone and low
values for serum 17-alpha-hydroxyproges-
terone (<0.2 ng/mL).
III. Treatment
A. Treatment of primary amenorrhea is directed at
correcting the underlying pathology; helping the
woman to achieve fertility, if desired; and preven-
tion of complications of the disease.
B. Congenital anatomic lesions or Y chromo-
some material usually requires surgery. Surgical
correction of a vaginal outlet obstruction is neces-
sary before menarche, or as soon as the diagno-
sis is made after menarche. Creation of a
neovagina for patients with müllerian failure is
usually delayed until the women is emotionally
mature. If Y chromosome material is found,
gonadectomy should be performed to prevent
gonadal neoplasia. However, gonadectomy
should be delayed until after puberty in patients
with androgen insensitivity syndrome. These pa-
tients have a normal pubertal growth spurt and
feminize at the time of expected puberty.
C. Ovarian failure requires counseling about the
benefits and risks of hormone replacement ther-
apy.
D. Polycystic ovary syndrome is managed with
measures to reduce hirsutism, resume menses,
and fertility and prevent of endometrial hyperpla-
sia, obesity, and metabolic defects.
E. Functional hypothalamic amenorrhea can usu-
ally be reversed by weight gain, reduction in the
intensity of exercise, or resolution of illness or
emotional stress. For women who want to con-
tinue to exercise, estrogen-progestin replacement
therapy should be given to those not seeking
fertility to prevent osteoporosis. Women who want
to become pregnant can be treated with gonado-
tropins or pulsatile GnRH.
F. Hypothalamic or pituitary dysfunction that is
not reversible (eg, congenital GnRH deficiency) is
treated with either exogenous gonadotropins or
pulsatile GnRH if the woman wants to become
pregnant.
References: See page 208.

Secondary Amenorrhea
Amenorrhea (absence of menses) can be a transient,
intermittent, or permanent condition resulting from dys-
function of the hypothalamus, pituitary, ovaries, uterus,
or vagina. Amenorrhea is classified as either primary
(absence of menarche by age 16 years) or secondary
(absence of menses for more than three cycles or six
months in women who previously had menses). Preg-
nancy is the most common cause of secondary
amenorrhea.
I. Diagnosis of secondary amenorrhea
A. Step 1: Rule out pregnancy. A pregnancy test is
the first step in evaluating secondary amenorrhea.
Measurement of serum beta subunit of hCG is the
most sensitive test.
B. Step 2: Assess the history
1. Recent stress; change in weight, diet or exercise
habits; or illnesses that might result in hypotha-
lamic amenorrhea should be sought.
2. Drugs associated with amenorrhea, systemic
illnesses that can cause hypothalamic
amenorrhea, recent initiation or discontinuation
of an oral contraceptive, androgenic drugs
(danazol) or high-dose progestin, and
antipsychotic drugs should be evaluated.
3. Headaches, visual field defects, fatigue, or
polyuria and polydipsia may suggest
hypothalamic-pituitary disease.
4. Symptoms of estrogen deficiency include hot
flashes, vaginal dryness, poor sleep, or de-
creased libido.
5. Galactorrhea is suggestive of
hyperprolactinemia. Hirsutism, acne, and a his-
tory of irregular menses are suggestive of
hyperandrogenism.
6. A history of obstetrical catastrophe, severe
bleeding, dilatation and curettage, or
endometritis or other infection that might have
caused scarring of the endometrial lining sug-
gests Asherman's syndrome.
C. Step 3: Physical examination. Measurements of
height and weight, signs of other illnesses, and
evidence of cachexia should be assessed. The
skin, breasts, and genital tissues should be evalu-
ated for estrogen deficiency. The breasts should
be palpated, including an attempt to express
galactorrhea. The skin should be examined for
hirsutism, acne, striae, acanthosis nigricans,
vitiligo, thickness or thinness, and easy
bruisability.
D. Step 4: Basic laboratory testing. In addition to
measurement of serum hCG to rule out preg-
nancy, minimal laboratory testing should include
measurements of serum prolactin, thyrotropin,
and FSH to rule out hyperprolactinemia, thyroid
disease, and ovarian failure (high serum FSH). If
there is hirsutism, acne or irregular menses, se-
rum dehydroepiandrosterone sulfate (DHEA-S)
and testosterone should be measured.
E. Step 5: Follow-up laboratory evaluation
1. High serum prolactin concentration.
Prolactin secretion can be transiently increased
by stress or eating. Therefore, serum prolactin
should be measured at least twice before cra-
nial imaging is obtained, particularly in those
women with small elevations (<50 ng/mL).
These women should be screened for thyroid
disease with a TSH and free T4 because
hypothyroidism can cause hyperprolactinemia.
2. Women with verified high serum prolactin val-
ues should have a cranial MRI unless a very
clear explanation is found for the elevation (eg,
antipsychotics). Imaging should rule out a hy-
pothalamic or pituitary tumor.
3. High serum FSH concentration. A high se-
rum FSH concentration indicates the presence
of ovarian failure. This test should be repeated
monthly on three occasions to confirm. A
karyotype should be considered in most women
with secondary amenorrhea age 30 years or
younger.

Causes of Primary and Secondary Amenorrhea

Abnormality Causes

Pregnancy

Anatomic abnormalities

Congenital abnormality Isolated defect

in Müllerian development
Testicular feminization syn-
drome
5-Alpha-reductase defi-
ciency
Vanishing testes syndrome
Defect in testis determining
factor

Congenital defect of uro- Agenesis of lower vagina

genital sinus develop- Imperforate hymen
ment

Acquired ablation or Asherman’s syndrome

scarring of the Tuberculosis
endometrium

Disorders of
hypothalamic-pituitary
ovarian axis
Hypothalamic dysfunc-
tion
Pituitary dysfunction
Ovarian dysfunction

Causes of Amenorrhea due to Abnormalities in

the Hypothalamic-Pituitary-Ovarian Axis

Abnormality Causes

Hypothalamic dys- Functional hypothalamic

function amenorrhea
Weight loss, eating disorders
Exercise
Stress
Severe or prolonged illness
Congenital gonadotropin-releasing
hormone deficiency
Inflammatory or infiltrative diseases
Brain tumors - eg,
craniopharyngioma
Pituitary stalk dissection or com-
pression
Cranial irradiation
Brain injury - trauma, hemorrhage,
hydrocephalus
Other syndromes - Prader-Willi,
Laurence-Moon-Biedl

Pituitary dysfunction Hyperprolactinemia

Other pituitary tumors- acromegaly,
corticotroph adenomas (Cushing's
disease)
Other tumors - meningioma,
germinoma, glioma
Empty sella syndrome
Pituitary infarct or apoplexy

Ovarian dysfunction Ovarian failure (menopause)

Spontaneous
Premature (before age 40
years)
Surgical

Other Hyperthyroidism
Hypothyroidism
Diabetes mellitus
Exogenous androgen use

Drugs Associated with Amenorrhea

Drugs that Increase Antipsychotics

Prolactin Tricyclic antidepressants
Calcium channel blockers

Drugs with Estro- Digoxin, marijuana, oral contracep-

genic Activity tives

Drugs with Ovarian Chemotherapeutic agents

Toxicity
 4. High serum androgen concentrations. A high
serum androgen value may suggest the diagno-
sis of polycystic ovary syndrome or may suggest
an androgen-secreting tumor of the ovary or
adrenal gland. Further testing for a tumor might
include a 24-hour urine collection for cortisol
and 17-ketosteroids, determination of serum 17-
hydroxyprogesterone after intravenous injection
of corticotropin (ACTH), and a dexamethasone
suppression test. Elevation of 17-ketosteroids,
DHEA-S, or 17-hydroxyprogesterone is more
consistent with an adrenal, rather than ovarian,
source of excess androgen.
5. Normal or low serum gonadotropin concen-
trations and all other tests normal
a. This result is one of the most common out-
comes of laboratory testing in women with
amenorrhea. Women with hypothalamic
amenorrhea (caused by excessive exercise
or weight loss) have normal to low serum
FSH values. Cranial MRI is indicated in all
women without an a clear explanation for
hypogonadotropic hypogonadism and in
most women who have visual field defects or
headaches. No further testing is required if
the onset of amenorrhea is recent or is easily
explained (eg, weight loss, excessive exer-
cise) and there are no symptoms suggestive
of other disease.
b. High serum transferrin saturation may indi-
cate hemochromatosis, high serum
angiotensin-converting enzyme values sug-
gest sarcoidosis, and high fasting blood glu-
cose or hemoglobin A1c values indicate dia-
betes mellitus.
6. Normal serum prolactin and FSH concentra-
tions with history of uterine instrumentation
preceding amenorrhea
a. Evaluation for Asherman's syndrome should
be completed. A progestin challenge should
be performed (medroxyprogesterone acetate
10 mg for 10 days). If withdrawal bleeding
occurs, an outflow tract disorder has been
ruled out. If bleeding does not occur, estro-
gen and progestin should be administered.
b. Oral conjugated estrogens (0.625 to 2.5 mg
daily for 35 days) with medroxyprogesterone
added (10 mg daily for days 26 to 35); failure
to bleed upon cessation of this therapy
strongly suggests endometrial scarring. In
this situation, a hysterosalpingogram or
hysteroscopy can confirm the diagnosis of
Asherman syndrome.
II. Treatment
A. Athletic women should be counseled on the need
for increased caloric intake or reduced exercise.
Resumption of menses usually occurs.
B. Nonathletic women who are underweight
should receive nutritional counseling and treatment
of eating disorders.
C. Hyperprolactinemia is treated with a dopamine
agonist. Cabergoline (Dostinex) or bromocriptine
(Parlodel) are used for most adenomas. Ovulation,
regular menstrual cycles, and pregnancy may usu-
ally result.
D. Ovarian failure should be treated with hormone
replacement therapy.
E. Hyperandrogenism is treated with measures to
reduce hirsutism, resume menses, and fertility and
preventing endometrial hyperplasia, obesity, and
metabolic defects.
F. Asherman's syndrome is treated with
hysteroscopic lysis of adhesions followed by long-
term estrogen administration to stimulate regrowth
of endometrial tissue.
References: See page 208.

Menopause
Menopause is defined as the cessation of menstrual
periods, menopause occurs at a mean age of 51.4 years
in normal women.
I. Definitions
A. Menopausal transition begins with variation in
menstrual cycle length and an elevated FSH con-
centration and ends with the final menstrual period
(12 months of amenorrhea). Stage -2 (early) is
characterized by variable cycle length (>7 days
different from normal menstrual cycle length,
which is 21 to 35 days). Stage -1 (late) is charac-
terized by >2 skipped cycles and an interval of
amenorrhea >60 days; women at this stage often
have hot flashes as well.
B. Perimenopause begins in stage -2 of the meno-
pausal transition and ends 12 months after the last
menstrual period.
C. Menopause is defined by 12 months of
amenorrhea after the final menstrual period. It
results from complete, or near complete, ovarian
follicular depletion and absence of ovarian estro-
gen secretion.
D. Postmenopause. Stage +1 (early) is defined as
the first five years after the final menstrual period.
It is characterized by further and complete decline
in ovarian function and accelerated bone loss;
many women in this stage continue to have hot
flashes. Stage +2 (late) begins five years after the
final menstrual period and ends with death.
II. Epidemiology
A. The average age at menopause is 51 years; how-
ever, for 5% of women it occurs after age 55 (late
menopause), and for another 5%, between ages
40 to 45 years (early menopause). Menopause
that occurs before age 40 years is premature ovar-
ian failure.
B. The age of menopause is reduced by about two
years in women who smoke. Women who have
never had children and who have had regular
cycles tend to have an earlier age of menopause.
III. Clinical manifestations
A. Bleeding patterns. Chronic anovulation and pro-
gesterone deficiency in this transition period may
cause long periods of unopposed estrogen expo-
sure and result in anovulatory bleeding and
endometrial hyperplasia.
B. Oligomenorrhea (irregular cycles) for six or more
months, or an episode of heavy dysfunctional
bleeding is an indication for endometrial surveil-
lance. Endometrial biopsy is the standard to rule
out the occurrence of endometrial hyperplasia.
C. Irregular or heavy bleeding during the meno-
pausal transition may be treated with low-dose oral
contraceptives or intermittent progestin therapy.
D. Hot flashes
1. The most common symptom during menopause
is the hot flash, occurring in up to 75%. Hot
flashes are self-limited, usually resolving with-
out treatment within one to five years, although
some women will continue to have hot flashes
until after age 70.
2. Hot flashes begin as the sudden sensation of
heat in the upper chest and face that rapidly
becomes generalized. The sensation of heat
lasts from two to four minutes, is often associ-
ated with perspiration and occasionally palpita-
tions, and is often followed by chills and shiver-
ing, and sometimes anxiety. Hot flashes usually
occur several times per day and are common at
night.
E. Genitourinary symptoms
1. Vaginal dryness. The vagina and urethra are
very sensitive to estrogen, and estrogen defi-
ciency leads to thinning of the vaginal epithe-
lium. This results in vaginal atrophy (atrophic
vaginitis), causing symptoms of vaginal dry-
ness, itching and often, dyspareunia.
2. The vagina typically appears pale, with lack of
the normal rugae and often has visible blood
vessels or petechial hemorrhages.
3. Sexual dysfunction. Estrogen deficiency
causes a decrease in blood flow to the vagina
and vulva, decreased vaginal lubrication, and
sexual dysfunction.
4. Atrophic urethritis results from low estrogen
production after the menopause, predisposing
to stress and urge urinary incontinence. The
prevalence of incontinence increases with age.
IV. Diagnosis
A. Menopause is defined as 12 months of
amenorrhea in a woman over age 45 in the ab-
sence of other causes. Further evaluation is not
necessary for women in this group.
B. The best approach to diagnosing the menopausal
transition is an assessment of menstrual cycle
history and menopausal symptoms (vasomotor
flushes, mood changes, sleep disturbances). Mea-
suring serum FSH, estradiol, or inhibin levels is
usually not necessary. Serum FSH concentrations
increase across the menopausal transition, but at
times may be suppressed into the normal
premenopausal range (after a recent ovulation).
C. Differential diagnosis. Hyperthyroidism should
be considered in the differential diagnosis because
irregular menses, sweats (although different from
typical hot flashes), and mood changes are all
potential clinical manifestations of hyperthyroidism.
Other etiologies for menstrual cycle changes that
should be considered include pregnancy,
hyperprolactinemia, and thyroid disease. Atypical
hot flashes and night sweats may be caused by
medications, carcinoid, pheochromocytoma, or
underlying malignancy.
V. Treatment of menopausal symptoms in women
not taking systemic estrogen
A. Many women cannot or choose not to take estro-
gen to treat symptoms of estrogen deficiency at
menopause because of an increased risk of breast
cancer and cardiovascular disease.
B. Therapy prevents bone loss and fracture, but does
not confir a protective effect on the heart. Continu-
ous combined therapy with conjugated estrogen
(0.625 mg/day) and medroxyprogesterone acetate
(2.5 mg/day) is ineffective for either primary or
secondary prevention of CHD, and slightly in-
creases risk. Other risks included an increased
risk of stroke, venous thromboembolism, and
breast cancer.
C. Patient selection. Estrogen is a reasonable short-
term option for most symptomatic postmenopausal
women, with the exception of those with a history
of breast cancer, coronary heart disease, a previ-
ous venous thromboembolic event or stroke, or
those at high risk for these complications. Short-
term therapy is six months to five years.
D. Vasomotor instability. Hot flashes can result in
sleep disturbances, headache, and irritability. Al-
though estrogen is the gold standard for relief of
hot flashes, a number of other drugs have been
shown to be somewhat better than placebo.
Venlafaxine (Effexor, 75 mg daily) reduces hot
flashes by 61%. Mouth dryness, anorexia, nausea,
and constipation are common. Gabapentin
(Neurontin) has been used for hot flashes at a
dose of 200mg orally once daily to 400mg orally
four times daily.
E. Urogenital atrophy
1. Both systemic and vaginal estrogen are effec-
tive for genitourinary atrophy; however, vaginal
estrogen has lesser systemic levels than estro-
gen tablets.
2. Moisturizers and lubricants. The long-acting
vaginal moisturizer, Replens, produces a moist
film over the vaginal tissue. A water soluble
lubricant, such as Astroglide and K-Y Personal
Lubricant, should be used at the time of inter-
course.
3. Low-dose vaginal estrogen
a. Estrogen Cream (Premarin) 0.5 g of cream,
or one-eighth of an applicatorful daily into the
vagina for three weeks followed by twice
weekly administration thereafter. Estrace,
which is crystalline estradiol, can also by
given by vaginal applicator at a dose of one-
eighth of an applicator or 0.5 g (which con-
tains 50 microgram of estradiol).
b. Vaginal ring is a silastic ring impregnated
with estradiol (Estring, Phadia) involves in-
sertion of a silastic ring that delivers 6 to 9
mcg of estradiol to the vagina daily for a pe-
riod of three months.
c. With low-dose vaginal estrogen, a progestin
is not necessary.
F. Osteoporosis. Estrogen is no longer a primary
therapy for osteoporosis. Exercise, and daily in-
take of calcium (1500 mg/day) and vitamin D (400
to 800 IU/day) are recommended for prevention of
bone loss in perimenopausal and postmenopausal
women.
VI. Treatment of menopausal symptoms with hor-
mone therapy
A. Estrogen prevents bone loss and fracture, but is
not cardioprotective, and slightly increases risk.
Other risks seen with combined therapy included
an increased risk of stroke, venous
thromboembolism, and breast cancer.
B. Menopausal symptoms
1. Hot flashes. Estrogen therapy remains the gold
standard for relief of menopausal symptoms, in
particular, hot flashes, and therefore is a rea-
sonable option for most postmenopausal
women, with the exception of those with a his-
tory of breast cancer, CHD, a previous venous
thromboembolic event or stroke, or those at
high risk for these complications. In otherwise
healthy women, the absolute risk of an adverse
event is extremely low.
2. Short-term therapy (with a goal of symptom
management) is less than five years.
 3. Adding a progestin. Endometrial hyperplasia
and cancer can occur after as little as six
months of unopposed estrogen therapy; as a
result, a progestin should be added in women
who have not had a hysterectomy. Women who
have undergone hysterectomy should not re-
ceive a progestin.
4. Hormone preparations: Combined, continuous
conjugated estrogens (0.625 mg) and
medroxyprogesterone acetate (MPA 2.5 mg) is
commonly used. However, low dose estrogen is
a better option (eg, 0.3 mg conjugated
estrogens or 0.5 mg estradiol).
5. A low-estrogen oral contraceptive (20 mcg of
ethinyl estradiol) remains an appropriate treat-
ment for perimenopausal women who seek
relief of menopausal symptoms, and who also
desire contraception, and in some instances
need bleeding control (in cases of dysfunctional
uterine bleeding). Most of these women are
between the ages of 40 and 50 years and are
still candidates for oral contraception.
6. When women taking a low-dose oral contracep-
tive during menopause reach age 50 or 51
years, options include stopping the pill alto-
gether, or changing to an estrogen replacement
regimen if necessary for symptoms. Tapering
the oral contraceptive by one pill per week is
recommended.
References: See page 208.

Premenstrual Syndrome and

Premenstrual Dysphoric Disorder
Premenstrual syndrome (PMS) is characterized by phys-
ical and behavioral symptoms that occur repetitively in
the second half of the menstrual cycle and interfere with
some aspects of the woman's life. Premenstrual
dysphoric disorder (PMDD) is the most severe form of
PMS, with the prominence anger, irritability, and internal
tension. PMS affects up to 75% of women with regular
menstrual cycles, while PMDD affects only 3 to 8% of
women.
I. Symptoms
A. The most common physical manifestation of PMS
is abdominal bloating, which occurs in 90% of
women with this disorder; breast tenderness and
headaches are also common, occurring in more
than 50% of cases.
B. The most common behavioral symptom of PMS is
an extreme sense of fatigue which is seen in more
than 90%. Other frequent behavioral complaints
include irritability, tension, depressed mood, labile
mood (80%), increased appetite (70%), and forget-
fulness and difficulty concentrating (50%).

Symptom Clusters Commonly Noted in Patients

with PMS

Affective Symptoms Cognitive or performance

Depression or sadness Mood instability or mood
Irritability swings
Tension Difficulty in concentrating
Anxiety Decreased efficiency
Tearfulness or crying easily Confusion
Restlessness or jitteriness Forgetfulness
Anger Accident-prone
Loneliness Social avoidance
Appetite change Temper outbursts
Food cravings Energetic
Changes in sexual interest Fluid retention
Pain Breast tenderness or swell-
Headache or migraine ing
Back pain Weight gain
Breast pain Abdominal bloating or swell-
Abdominal cramps ing
General or muscular pain Swelling of extremities
General somatic
Fatigue or tiredness
Dizziness or vertigo
Nausea
Insomnia

C. Other common findings include acne,

oversensitivity to environmental stimuli, anger, easy
crying, and gastrointestinal upset. Hot flashes,
heart palpitations, and dizziness occur in 15 to 20%
of patients. Symptoms should occur in the luteal
phase only.

UCSD Criteria for Premenstrual Syndrome

At least one of the following affective and somatic symptoms

during the five days before menses in each of the three
previous cycles:
Affective symptoms: depression, angry outbursts, irritability,
anxiety, confusion, social withdrawal
Somatic symptoms: breast tenderness, abdominal bloating,
headache, swelling of extremities Symptoms relieved from
days 4 through 13 of the menstrual cycle

DSM-IV Criteria for Premenstrual Dysphoric Dis-

order

• Five or more symptoms

• At least one of the following four symptoms:
Markedly depressed mood, feelings of hopelessness,
or self-deprecating thoughts
Marked anxiety, tension, feeling of being "keyed up" or
"on edge"
Marked affective lability
Persistent and marked anger or irritability or increase in
interpersonal conflicts
• Additional symptoms that may be used to fulfill the criteria:
Decreased interest in usual activities
Subjective sense of difficulty in concentrating
Lethargy, easy fatigability, or marked lack of energy
Marked change in appetite, overeating, or specific food
cravings
Hypersomnia or insomnia
Subjective sense of being overwhelmed or out of con-
trol
• Other physical symptoms such as breast tenderness or
swelling, headaches, joint or muscle pain, a sensation of
bloating, or weight gain
• Symptoms occurring during last week of luteal phase
• Symptoms are absent postmenstrually
• Disturbances that interfere with work or school or with
usual social activities and relationships
• Disturbances that are not an exacerbation of symptoms of
another disorder

Differential Diagnosis of Premenstrual Syndrome

Affective disorder (eg, Endometriosis

depression, anxiety,
dysthymia, panic)
Anemia
Anorexia or bulimia
Chronic medical conditions
(eg, diabetes mellitus)
Dysmenorrhea
Hypothyroidism
Oral contraceptive pill use
Perimenopause
Personality disorder
Substance abuse disorders

D. Differential diagnosis
1. PMDD should be differentiated from
premenstrual exacerbation of an underlying
major psychiatric disorder, as well as medical
conditions such as hyper- or hypothyroidism.
2. About 13% of women with PMS are found to
have a psychiatric disorder alone with no evi-
dence of PMS, while 38% had premenstrual
exacerbation of underlying depressive and anx-
iety disorders.
3. 39% of women with PMDD meet criteria for
mood or anxiety disorders.
4. The assessment of patients with possible PMS
or PMDD should begin with the history, physical
examination, chemistry profile, complete blood
count, and serum TSH. The history should fo-
cus in particular on the regularity of menstrual
cycles. Appropriate gynecologic endocrine eval-
uation should be performed if the cycles are
irregular (lengths less than 25 or >36 days).
5. The patient should be asked to record symp-
toms prospectively for two months. If the patient
fails to demonstrate a symptom free interval in
the follicular phase, she should be evaluated
for a mood or anxiety disorder.
II. Nonpharmacologic therapy
A. Relaxation therapy and cognitive behavioral ther-
apy have shown some benefit. Behavioral mea-
sures include keeping a symptom diary, getting
adequate rest and exercise, and making dietary
changes.
B. Sleep disturbances, ranging from insomnia to
excessive sleep, are common. A structured sleep
schedule with consistent sleep and wake times is
recommended. Sodium restriction may minimize
bloating, fluid retention, and breast swelling and
tenderness. Caffeine restriction and aerobic exer-
cise often reduce symptoms.
III. Dietary Supplementation
A. Vitamin E supplementation is a treatment for
mastalgia. The administration of 400 IU per day of
vitamin E during the luteal phase improves affec-
tive and somatic symptoms.
B. Calcium carbonate in a dosage of 1200 mg per
day for three menstrual cycles results in symptom
improvement in 48% of women with PMS.
IV. Pharmacologic Therapy
A. Fluoxetine (Sarafem) and sertraline (Zoloft) have
been approved for the treatment of PMDD. SSRIs
are recommended as initial drug therapy in women
with PMS and PMDD. Common side effects of
SSRIs include insomnia, drowsiness, fatigue, nau-
sea, nervousness, headache, mild tremor, and
sexual dysfunction.
B. Fluoxetine (Sarafem) 20 mg or sertraline (Zoloft)
50 mg, taken in the morning, is best tolerated and
sufficient to improve symptoms. Fluoxetine or
sertraline can be given during the 14 days before
the menstrual period.
C. Benefit has also been demonstrated for citalopram
(Celexa) during the 14 days before the menstrual
period.
D. Diuretics. Spironolactone (Aldactone) is the only
diuretic that has been shown to effectively relieve
breast tenderness and fluid retention.
Spironolactone is administered only during the
luteal phase.
E. Prostaglandin Inhibitors. Nonsteroidal
anti-inflammatory drugs (NSAIDs) are traditional
therapy for primary dysmenorrhea and
menorrhagia. These agents include mefenamic
acid (Ponstel) and naproxen sodium (Anaprox,
Aleve).
References: See page 208.

Prescription Medications Commonly Used in the

Treatment of Premenstrual Syndrome (PMS)

Drug
class and
represen- Recom-
tative mendatio Side ef-
agents Dosage ns fects

SSRIs

Fluoxetine 10 to 20 First-choic Insomnia,

(Sarafem) mg per e agents drowsi-
day for the ness, fa-
treatment tigue, nau-
Sertraline 50 to 150 of PMDD. sea, ner-
(Zoloft) mg per Effective vousness,
day in alleviat- headache,
ing behav- mild
ioral and tremor,
Paroxetine 10 to 30 physical sexual
(Paxil) mg per symptoms dysfunc-
day of PMS tion
and PMDD
Fluvoxami 25 to 50 Administer
ne (Luvox) mg per during
day luteal
phase (14
days be-
Citalopram 20 to 40 fore men-
(Celexa) mg per ses).
day

Diuretics

Spironolac 25 to 100 Effective Antiestrog

tone mg per in alleviat- enic ef-
(Aldactone day luteal ing breast fects,
) phase tender- hyperkale
ness and mia
bloating.

NSAIDs

Naproxen 275 to 550 Effective Nausea,

sodium mg twice in alleviat- gastric
(Anaprox) daily ing various ulceration,
physical renal dys-
symptoms function.
of PMS. Use with
Any caution in
Mefenami 250 mg tid NSAID women
c acid with meals should be with preex-
(Ponstel) effective. isting gas-
trointestina
l or renal
disease.

Androgens

Danazol 100 to 400 Somewhat Weight

(Danocrine mg twice effective in gain, de-
) daily alleviating creased
mastalgia breast
when size, deep-
taken dur- ening of
 Drug
class and
represen- Recom-
tative mendatio Side ef-
agents Dosage ns fects

ing luteal voice.

phase. Monitor
lipid profile
and liver
function.

GnRH agonists

Leuprolide 3.75 mg Somewhat Hot

(Lupron) IM every effective in flashes,
month or alleviating cardiovas-
11.25 mg physical cular ef-
IM every and be- fects, and
three havioral osteoporo-
months symptoms sis
of PMS
Side effect
profile and
cost limit
use.

Goserelin 3.6 mg SC
(Zoladex) every
month or
10.8 mg
SC every
three
months

Nafarelin 200 to 400

(Synarel) mcg
intranasall
y twice
daily

Abnormal Vaginal Bleeding

Menorrhagia (excessive bleeding) is most commonly
caused by anovulatory menstrual cycles. Occasionally it
is caused by thyroid dysfunction, infections or cancer.
I. Pathophysiology of normal menstruation
A. In response to gonadotropin-releasing hormone
from the hypothalamus, the pituitary gland synthe-
sizes follicle-stimulating hormone (FSH) and
luteinizing hormone (LH), which induce the ovaries
to produce estrogen and progesterone.
B. During the follicular phase, estrogen stimulation
causes an increase in endometrial thickness. After
ovulation, progesterone causes endometrial matu-
ration. Menstruation is caused by estrogen and
progesterone withdrawal.
C. Abnormal bleeding is defined as bleeding that
occurs at intervals of less than 21 days, more than
36 days, lasting longer than 7 days, or blood loss
>80 mL.
II. Clinical evaluation of abnormal vaginal bleed-
ing
A. A menstrual and reproductive history should in-
clude last menstrual period, regularity, duration,
frequency; the number of pads used per day, and
intermenstrual bleeding.
B. Stress, exercise, weight changes and systemic
diseases, particularly thyroid, renal or hepatic dis-
eases or coagulopathies, should be sought. The
method of birth control should be determined.
C. Pregnancy complications, such as spontaneous
abortion, ectopic pregnancy, placenta previa and
abruptio placentae, can cause heavy bleeding.
Pregnancy should always be considered as a pos-
sible cause of abnormal vaginal bleeding.
III. Puberty and adolescence – menarche to age 16
A. Irregularity is normal during the first few months of
menstruation; however, soaking more than 25
pads or 30 tampons during a menstrual period is
abnormal.
B. Absence of premenstrual symptoms (breast ten-
derness, bloating, cramping) is associated with
anovulatory cycles.
C. Fever, particularly in association with pelvic or
abdominal pain may, indicate pelvic inflammatory
disease. A history of easy bruising suggests a
coagulation defect. Headaches and visual changes
suggest a pituitary tumor.
D. Physical findings
1. Pallor not associated with tachycardia or signs
of hypovolemia suggests chronic excessive
blood loss secondary to anovulatory bleeding,
adenomyosis, uterine myomas, or blood
dyscrasia.
2. Fever, leukocytosis, and pelvic tenderness sug-
gests PID.
3. Signs of impending shock indicate that the blood
loss is related to pregnancy (including ectopic),
trauma, sepsis, or neoplasia.
4. Pelvic masses may represent pregnancy, uter-
ine or ovarian neoplasia, or a pelvic abscess or
hematoma.
5. Fine, thinning hair, and hypoactive reflexes sug-
gest hypothyroidism.
6. Ecchymoses or multiple bruises may indicate
trauma, coagulation defects, medication use, or
dietary extremes.
E. Laboratory tests
1. CBC and platelet count and a urine or serum
pregnancy test should be obtained.
2. Screening for sexually transmitted diseases,
thyroid function, and coagulation disorders (par-
tial thromboplastin time, INR, bleeding time)
should be completed.
3. Endometrial sampling is rarely necessary for
those under age 20.
F. Treatment of infrequent bleeding
1. Therapy should be directed at the underlying
cause when possible. If the CBC and other initial
laboratory tests are normal and the history and
physical examination are normal, reassurance is
usually all that is necessary.
2. Ferrous gluconate, 325 mg bid-tid, should be
prescribed.
G. Treatment of frequent or heavy bleeding
1. Treatment with nonsteroidal anti-inflammatory
drugs (NSAIDs) improves platelet aggregation
and increases uterine vasoconstriction. NSAIDs
are the first choice in the treatment of
menorrhagia because they are well tolerated
and do not have the hormonal effects of oral
contraceptives.
a. Mefenamic acid (Ponstel) 500 mg tid during
the menstrual period.
b. Naproxen (Anaprox, Naprosyn) 500 mg
loading dose, then 250 mg tid during the
menstrual period.
c. Ibuprofen (Motrin, Nuprin) 400 mg tid dur-
ing the menstrual period.
d. Gastrointestinal distress is common. NSAIDs
are contraindicated in renal failure and peptic
ulcer disease.
2. Iron should also be added as ferrous gluconate
325 mg tid.
H. Patients with hypovolemia or a hemoglobin
level below 7 g/dL should be hospitalized for hor-
monal therapy and iron replacement.
1. Hormonal therapy consists of estrogen
(Premarin) 25 mg IV q6h until bleeding stops.
Thereafter, oral contraceptive pills should be
administered q6h x 7 days, then taper slowly to
one pill qd.
2. If bleeding continues, IV vasopressin (DDAVP)
should be administered. Hysteroscopy may be
necessary, and dilation and curettage is a last
resort. Transfusion may be indicated in severe
hemorrhage.
3. Iron should also be added as ferrous gluconate
325 mg tid.
IV. Primary childbearing years – ages 16 to early
40s
A. Contraceptive complications and pregnancy are
the most common causes of abnormal bleeding in
this age group. Anovulation accounts for 20% of
cases.
B. Adenomyosis, endometriosis, and fibroids increase
in frequency as a woman ages, as do endometrial
hyperplasia and endometrial polyps. Pelvic inflam-
matory disease and endocrine dysfunction may
also occur.
C. Laboratory tests
1. CBC and platelet count, Pap smear, and preg-
nancy test.
2. Screening for sexually transmitted diseases,
thyroid-stimulating hormone, and coagulation
disorders (partial thromboplastin time, INR,
bleeding time).
3. If a non-pregnant woman has a pelvic mass,
ultrasonography or hysterosonography (with
uterine saline infusion) is required.
D. Endometrial sampling
1. Long-term unopposed estrogen stimulation in
anovulatory patients can result in endometrial
hyperplasia, which can progress to adeno-
carcinoma; therefore, in perimenopausal pa-
tients who have been anovulatory for an ex-
tended interval, the endometrium should be
biopsied.
2. Biopsy is also recommended before initiation of
hormonal therapy for women over age 30 and
for those over age 20 who have had prolonged
bleeding.
3. Hysteroscopy and endometrial biopsy with a
Pipelle aspirator should be done on the first day
of menstruation (to avoid an unexpected preg-
nancy) or anytime if bleeding is continuous.
E. Treatment
1. Medical protocols for anovulatory bleeding (dys-
functional uterine bleeding) are similar to those
described above for adolescents.
2. Hormonal therapy
a. In women who do not desire immediate fertil-
ity, hormonal therapy may be used to treat
menorrhagia.
b. A 21-day package of oral contraceptives is
used. The patient should take one pill three
times a day for 7 days. During the 7 days of
therapy, bleeding should subside, and, fol-
lowing treatment, heavy flow will occur. After
7 days off the hormones, another 21-day
package is initiated, taking one pill each day
for 21 days, then no pills for 7 days.
c. Alternatively, medroxyprogesterone
(Provera), 10-20 mg per day for days 16
through 25 of each month, will result in a re-
duction of menstrual blood loss. Pregnancy
will not be prevented.
d. Patients with severe bleeding may have
hypotension and tachycardia. These patients
require hospitalization, and estrogen
(Premarin) should be administered IV as 25
mg q4-6h until bleeding slows (up to a maxi-
mum of four doses). Oral contraceptives
should be initiated concurrently as described
above.
3. Iron should also be added as ferrous gluconate
325 mg tid.
4. Surgical treatment can be considered if child-
bearing is completed and medical management
fails to provide relief.
V. Premenopausal, perimenopausal, and
postmenopausal years--age 40 and over
A. Anovulatory bleeding accounts for about 90% of
abnormal vaginal bleeding in this age group. How-
ever, bleeding should be considered to be from
cancer until proven otherwise.
B. History, physical examination and laboratory test-
ing are indicated as described above. Meno-
pausal symptoms, personal or family history of
malignancy and use of estrogen should be
sought. A pelvic mass requires an evaluation with
ultrasonography.
C. Endometrial carcinoma
1. In a perimenopausal or postmenopausal wom-
an, amenorrhea preceding abnormal bleeding
suggests endometrial cancer. Endometrial
evaluation is necessary before treatment of
abnormal vaginal bleeding.
2. Before endometrial sampling, determination of
endometrial thickness by transvaginal
ultrasonography is useful because biopsy is
often not required when the endometrium is
less than 5 mm thick.
D. Treatment
1. Cystic hyperplasia or endometrial hyperplasia
without cytologic atypia is treated with depo-
medroxyprogesterone, 200 mg IM, then 100 to
200 mg IM every 3 to 4 weeks for 6 to 12
months. Endometrial hyperplasia requires re-
peat endometrial biopsy every 3 to 6 months.
2. Atypical hyperplasia requires fractional dilation
and curettage, followed by progestin therapy or
hysterectomy.
3. If the patient's endometrium is normal (or atro-
phic) and contraception is a concern, a low-
dose oral contraceptive may be used. If contra-
ception is not needed, estrogen and progester-
one therapy should be prescribed.
4. Surgical management
a. Vaginal or abdominal hysterectomy is the
most absolute curative treatment.
b. Dilatation and curettage can be used as a
temporizing measure to stop bleeding.
c. Endometrial ablation and resection by
laser, electrodiathermy “rollerball,” or
excisional resection are alternatives to
hysterectomy.
References: See page 208.
Endometrial Hyperplasia
Endometrial hyperplasia is an endmetrial abnormality
characterized by abnormal proliferation of endometrial
glands, resulting in an increased gland-to-stroma ratio.
The proliferating glands vary in size and shape and may
show cytological atypia, which may progress to
endometrial cancer. Endometrial hyperplasia is caused
by chronic estrogen stimulation unopposed by the coun-
terbalancing effects of progesterone.

I. Classification
A. The World Health Organization classification of
endometrial hyperplasia is based upon two fac-
tors:
1. Simple or complex glandular/stromal architec-
tural pattern
2. The presence or absence of nuclear atypia
B. Simple versus complex. Simple hyperplasia is
characterized by glands that are cystically dilated
with only occasional outpouching; mitoses of the
glandular cells may be present.
C. Complex hyperplasia consists of endometrial
glands that are back-to-back with luminal
outpouching and minimal intervening stroma. The
gland-to-stroma ratio is higher in complex com-
pared to simple hyperplasia.
D. Atypia. Simple atypical hyperplasia is character-
ized by atypical cells lining glands that are sepa-
rated by significant amounts of normal stroma.
Complex atypical hyperplasia consists of back-to-
back crowding of glands lined by atypical cells.
E. Women with simple hyperplasia without atypia are
least likely to develop endometrial carcinoma,
whereas women with complex hyperplasia with
atypia are most likely to develop carcinoma.
F. Endometrial carcinoma is more than 10-fold more
likely in atypical hyperplasia (simple or complex).
Cancer occurs after a diagnosis of simple, com-
plex, simple atypical, and complex atypical hyper-
plasia in 1, 3, 8, and 29% of cases, respectively.
II. Risk factors for endometrial hyperplasia are the
same as those for endometrial cancer. The risk for
both disorders is increased 10-fold in women who use
unopposed estrogen replacement therapy.

Risk factors for Endometrial Cancer

Risk factor Relative risk (RR)

Increasing age NA
Unopposed estrogen ther- 2-10
apy 2
Late menopause (after age 2
55) 3
Nulliparity
Polycystic ovary syndrome 2-4
(chronic anovulation) 3
Obesity
Diabetes

Hereditary nonpolyposis 22-50% lifetime risk

colorectal cancer
Tamoxifen 2/1000

Early menarche NA
Estrogen secreting tumor NA
Family history of NA
endometrial, ovarian,
breast, or colon cancer

III. Etiology. Exposure of the endometrium to continu-

ous estrogen unopposed by progesterone can lead
to endometrial hyperplasia.
A. Endogenous estrogen. The most common
cause of endogenous unopposed estrogen is
chronic anovulation. Chronic anovulation is asso-
ciated with the polycystic ovary syndrome
(PCOS) and the perimenopausal period. Exces-
sive estradiol from an ovarian tumor (eg,
granulosa cell tumor) may also cause
endometrial hyperplasia.
B. Obese women have high levels of endogenous
estrogen resulting from conversion of
androstenedione to estrone and of androgens to
estradiol.
C. Exogenous estrogen. Continuous exposure to
unopposed estrogen (0.625 mg of conjugated
estrogens orally daily) results in an increased
incidence of endometrial hyperplasia. 62% of
women who receive only estrogen develop
endometrial hyperplasia.
IV. Clinical manifestations. Endometrial hyperplasia
should be suspected in women with heavy, pro-
longed, frequent (ie, less than 21 days), or irregular
uterine bleeding. Abnormal uterine bleeding in
perimenopausal or postmenopausal women is the
most common clinical symptom of endometrial neo-
plasia, although such bleeding is usually (80%) due
to a benign condition. Postmenopausal bleeding
requires evaluation.
V. Diagnostic evaluation
A. Indications for endometrial biopsy
1. Abnormal uterine bleeding. An endometrial
biopsy should be performed in all women with
abnormal uterine bleeding in whom
endometrial hyperplasia or carcinoma is a
possibility
2. Atypical glandular cells detected by cervical
cytology should be investigated with an
endometrial biopsy to determine whether
endometrial hyperplasia or carcinoma is the
cause.
3. Endometrial cells. Asymptomatic women with
benign appearing endometrial cells noted on
cervical cytology should undergo endometrial
biopsy if they are at increased risk of
endometrial cancer (eg, postmenopausal;
family or personal history of ovarian, breast,
colon, or endometrial cancer; tamoxifen use;
chronic anovulation; obesity; estrogen therapy;
prior endometrial hyperplasia; diabetes).

Women Who Should Undergo Evaluation for

Endometrial Hyperplasia or Endometrial Cancer

Over age 40 years with abnormal uterine bleeding

Under age 40 years with abnormal uterine bleeding
and risk factors (eg, chronic anovulation, obesity,
tamoxifen)
Failure to respond to medical treatment of abnormal
uterine bleeding
Postmenopausal women with uterus receiving unop-
posed estrogen replacement therapy
Presence of atypical glandular cells on Papanicolaou
smear
Presence of endometrial cells on Papanicolaou
smear in a woman >40 year of age
Women with hereditary nonpolyposis colorectal
cancer

B. Indications for additional diagnostic evalua-

tion
1. Endometrial hyperplasia with atypia. If
endometrial hyperplasia with atypia is diag-
nosed by office biopsy, further evaluation is
needed to exclude a coexistent endometrial
adenocarcinoma, which is present in 25%.
Dilation and curettage (D&C) can be per-
formed to rule out endometrial cancer. Given a
risk of endometrial cancer of 35 to 43% in
these women, hysterectomy should be consid-
ered, especially in postmenopausal women or
those no longer considering future fertility.
2. Nondiagnostic office biopsy. Endometrial
hyperplasia/cancer needs to be excluded in
women with a nondiagnostic office biopsy.
Dilatation and curettage or hysteroscopy with
directed biopsy is required.
3. Persistent bleeding. Endometrial hyperpla-
sia/cancer needs to be excluded if abnormal
uterine bleeding persists after a benign
endometrial biopsy or treatment of
endometrial pathology. Transvaginal
sonography with or without
hysteroscopy/directed biopsy should be per-
formed to determine the cause of bleeding.
4. Postmenopausal women. Further diagnostic
evaluation of simple or complex endometrial
hyperplasia without atypia is unnecessary in
pre- or peri-menopausal women. Obesity can
be considered the probable etiology of
endometrial hyperplasia in menopausal
women.
VI. Treatment. Simple or complex endometrial hyper-
plasia without atypia is treated in order to control
abnormal uterine bleeding and to prevent progres-
sion to cancer, although this risk is very low (<1 to
3%). Atypical endometrial hyperplasia is treated for
the same reasons, except the risk of a subsequent
diagnosis of endometrial cancer is much higher (17
to 53%).
A. Premenopausal women
1. No atypia. Treatment consists of treatment
with progestins with follow-up sampling to doc-
ument regression. Medroxyprogesterone ace-
tate (MPA) 10 mg daily should be prescribed
for 12 to 14 days each month for three to six
months. Regression occurs in 80% with hyper-
plasia without atypia treated with MPA.
Micronized progesterone (100 to 200 mg) in a
vaginal cream is an alternative to MPA.
a. Ovulation induction is another option for
younger women with endometrial hyperpla-
sia without atypia who desire pregnancy.
b. Insertion of a levonorgestrel containing
intrauterine contraception (IUC) is also ef-
fective.
c. After treatment, preventative treatment
should be initiated if the patient has not
resumed normal cyclic menstrual function.
A rebiopsy is required if abnormal uterine
bleeding recurs.
2. With atypia. Endometrial hyperplasia with
atypia on initial endometrial biopsy is further
evaluated by D&C. If the diagnosis is con-
firmed and there is no coexistent
adenocarcinoma, treatment with continuous
oral megestrol acetate 40 mg twice per day
every day is initiated in women who wish to
preserve childbearing potential.
Medroxyprogesterone acetate 10 mg/day is an
alternative.
a. A repeat endometrial biopsy should be per-
formed in three months. Hysterectomy is
recommended if atypical hyperplasia per-
sists.
b. Once endometrial sampling has demon-
strated regression with no evidence of hy-
perplasia, the patient should pursue fertility
options. If childbearing is delayed, progestin
therapy should be continued. Options in-
clude megestrol acetate, MPA, oral contra-
ceptive pills, depot medroxyprogesterone
acetate, or a progestin releasing
intrauterine contraception. Repeating an
endometrial biopsy every 6 to 12 months
should be considered initially.
c. Hysterectomy is the treatment of choice for
women who are not planning future preg-
nancy or who are unable to comply with
medical therapy and follow-up endometrial
sampling.
B. Postmenopausal women
1. No atypia. If ovarian/adrenal tumors and use
of exogenous hormone therapy have been
excluded, treatment with continuous
medroxyprogesterone acetate (MPA) 10 mg
daily for three months should be started. An
endometrial biopsy should be performed im-
mediately after cessation of therapy. This regi-
men results in regression of simple and/or
complex endometrial hyperplasia to normal
endometrium after three months of therapy in
86%.
2. If follow-up endometrial biopsy shows per-
sistent endometrial hyperplasia without
atypia and the patient continues to have
bleeding, then a hysterectomy should be of-
fered or she can continue treatment with follow
up biopsies every 6 to 12 months. If
endometrial hyperplasia has regressed, then
treatment is discontinued.
3. If the woman is taking hormone replacement
therapy at diagnosis of endometrial hyperpla-
sia, the hormones should be discontinued and
MPA initiated as described above. If MPA
treatment is successful, and resumption of
hormone replacement therapy is desired, then
concurrent progestin treatment at higher
doses and for longer intervals is advised with
a repeat endometrial biopsy in three to six
months.
4. Postmenopausal women with endometrial
hyperplasia unrelated to exogenous estrogen
or an ovarian neoplasm are often obese.
These patients should lose weight and be
treated with MPA as described above.
5. With atypia. Endometrial hyperplasia with
atypia is considered a premalignant condition,
preferably treated with hysterectomy. If hyster-
ectomy is not an option, continuous oral
megestrol acetate at doses of 40 mg two to
four times per day (or MPA 10 mg/day) can be
administered after coexistent endometrial can-
cer has been excluded by hysteroscopy with
 directed biopsies. An endometrial biopsy
should be performed after three months of
therapy.

Options for Progestin Treatment for Prevention

of Endometrial Hyperplasia

Oral contraceptive pills

Levonorgestrel-releasing intrauterine device
Depot medroxyprogesterone acetate (150 mg IM)
every three months
Intermittent progestin therapy taken daily for 12-14
days per month:
medroxyprogesterone acetate (5-10 mg)
norethindrone acetate (5-15 mg)
micronized progesterone in a vaginal cream
(100-200 mg)
Continuous combined estrogen replacement therapy

Progestin Treatment of Endometrial Hyperplasia

Without Atypia

Medroxyprogesterone acetate (MPA) 10 mg daily for

12-14 days each month for 3-6 months
Micronized progesterone 100-200 mg daily in a vagi-
nal cream for 12-14 days each month for 3-6 months
Insertion of a levonorgestrel containing intrauterine
device

References: See page 208.

Breast Cancer Screening and Diag-

nosis
Breast cancer is the second most commonly diagnosed
cancer among women, after skin cancer. Approximately
182,800 new cases of invasive breast cancer are diag-
nosed in the United States per year. The incidence of
breast cancer increases with age. White women are
more likely to develop breast cancer than black women.
The incidence of breast cancer in white women is about
113 cases per 100,000 women and in black women, 100
cases per 100,000.
I. Risk factors

Risk Factors for Breast Cancer

Age >50 years Age >30 at first birth

Prior history of breast can- Obesity
cer High socioeconomic status
Family history Atypical hyperplasia on
Early menarche, before biopsy
age 12 Ionizing radiation exposure
Late menopause, after age
50
Nulliparity

A. Family history is highly significant in a first-degree

relative (ie, mother, sister, daughter), especially if
the cancer has been diagnosed premenopausally.
Women who have premenopausal first-degree
relatives with breast cancer have a three- to four-
fold increased risk of breast cancer. Having sev-
eral second-degree relatives with breast cancer
may further increase the risk of breast cancer.
Most women with breast cancer have no identifi-
able risk factors.
B. Approximately 8% of all cases of breast cancer
are hereditary. About one-half of these cases are
attributed to mutations in the BRCA1 and BRCA2
genes. Hereditary breast cancer commonly occurs
in premenopausal women. Screening tests are
available that detect BRCA mutations.
II. Diagnosis and evaluation
A. Clinical evaluation of a breast mass should
assess duration of the lesion, associated pain,
relationship to the menstrual cycle or exogenous
hormone use, and change in size since discovery.
The presence of nipple discharge and its charac-
ter (bloody or tea-colored, unilateral or bilateral,
spontaneous or expressed) should be assessed.
B. Menstrual history. The date of last menstrual
period, age of menarche, age of menopause or
surgical removal of the ovaries, previous pregnan-
cies should be determined.
C. History of previous breast biopsies, cyst aspira-
tion, dates and results of previous mammograms
should be determined.
D. Family history should document breast cancer in
relatives and the age at which family members
were diagnosed.
III. Physical examination
A. The breasts should be inspected for asymmetry,
deformity, skin retraction, erythema, peau
d'orange (breast edema), and nipple retraction,
discoloration, or inversion.
B. Palpation
1. The breasts should be palpated while the pa-
tient is sitting and then supine with the
ipsilateral arm extended. The entire breast
should be palpated systematically. The mass
should be evaluated for size, shape, texture,
tenderness, fixation to skin or chest wall.
2. mass that is suspicious for breast cancer is
usually solitary, discrete and hard. In some
instances, it is fixed to the skin or the muscle. A
suspicious mass is usually unilateral and
nontender. Sometimes, an area of thickening
may represent cancer. Breast cancer is rarely
bilateral. The nipples should be expressed for
discharge.
3. The axillae should be palpated for adenopathy,
with an assessment of size of the lymph nodes,
number, and fixation.
C. Mammography. Screening mammograms are
recommended every year for asymptomatic
women 40 years and older. Unfortunately, only
60% of cancers are diagnosed at a local stage.

Screening for Breast Cancer in Women

American Cancer Society guide-

Age lines

20 to 39 years Clinical breast examination every

three years
Monthly self-examination of breasts

Age 40 years Annual mammogram

and older Annual clinical breast examination
Monthly self-examination of breasts

IV. Methods of breast biopsy

A. Palpable masses. Fine-needle aspiration bi-
opsy (FNAB) has a sensitivity ranging from 90-
98%. Nondiagnostic aspirates require surgical
biopsy.
1. The skin is prepped with alcohol and the le-
sion is immobilized with the nonoperating
hand. A 10 mL syringe, with a 14 gauge nee-
dle, is introduced in to the central portion of
the mass at a 90E angle. When the needle
enters the mass, suction is applied by retract-
ing the plunger, and the needle is advanced.
The needle is directed into different areas of
the mass while maintaining suction on the
syringe.
2. Suction is slowly released before the needle is
withdrawn from the mass. The contents of the
needle are placed onto glass slides for patho-
logic examination.Excisional biopsy is done
when needle biopsies are negative but the
mass is clinically suspected of malignancy.
B. Stereotactic core needle biopsy. Using a
computer-driven stereotactic unit, the lesion is
localized in three dimensions, and an automated
biopsy needle obtains samples. The sensitivity
and specificity of this technique are 95-100% and
94-98%, respectively.
C. Nonpalpable lesions
1. Needle localized biopsy
a. Under mammographic guidance, a needle
and hookwire are placed into the breast
parenchyma adjacent to the lesion. The
patient is taken to the operating room along
with mammograms for an excisional breast
biopsy.
b. The skin and underlying tissues are infil-
trated with 1% lidocaine with epinephrine.
For lesions located within 5 cm of the nip-
ple, a periareolar incision may be used or
use a curved incision located over the mass
and parallel to the areola. Incise the skin
and subcutaneous fat, then palpate the
lesion and excise the mass.
c. After removal of the specimen, a specimen
x-ray is performed to confirm that the lesion
has been removed. The specimen can then
be sent fresh for pathologic analysis.
d. Close the subcutaneous tissues with a 4-0
chromic catgut suture, and close the skin
with 4-0 subcuticular suture.
2. Ultrasonography. Screening is useful to dif-
ferentiate between solid and cystic breast
masses when a palpable mass is not well
seen on a mammogram. Ultrasonography is
especially helpful in young women with dense
breast tissue when a palpable mass is not
visualized on a mammogram. Ultrasonography
is not used for routine screening because
microcalcifications are not visualized and the
yield of carcinomas is negligible.
References: See page 208.

Evaluation of Breast Lumps in Pri-

mary Care
About 16% of women ages 40 to 69 will have breast
complaints; the complaint is for a breast lump or lumpi-
ness in 40%. Breast cancer is found in 11% of women
complaining of a lump. Breast cancer is found in 8% of
abnormal screening mammograms and 2% of abnormal
screening clinical breast examinations. The vast majority
of breast lumps are caused by benign breast disease.
I. Diagnostic evaluation
A. History in women with a breast lump:
1. Its precise location
2. How it was first noted (accidentally, by breast
self-examination, clinical breast examination, or
mammogram)
3. How long it has been present
4. Presence of nipple discharge
5. Any change in size
6. Whether the lump waxes and wanes at times in
the menstrual cycle. Benign cysts may be more
prominent premenstrually and regress in size
during the follicular phase.
7. Assessment should evaluate past history of
breast cancer or breast biopsy, and risk factors
for breast cancer (eg, age, family history of
breast cancer, age of menarche, age at first
pregnancy, age at menopause, alcohol use,
and hormonal replacement therapy).
8. Older age, previous history of breast cancer,
and family history in a first degree relative in-
crease the chance that a palpable breast lump
is cancerous on biopsy.
B. Breast tissue in healthy women is often lumpy,
and sometimes general lumpiness, rather than a
distinct lump, is felt. The physical examination
should determine whether a dominant mass is
present.
C. If the initial physical examination does not confirm
the presence of a dominant mass, either the pa-
tient should be asked to return for a follow-up
examination in 2 to 3 months. Women who have
not had a mammogram in the preceding year and
are eligible for regular screening should have a
mammogram.
D. Classic characteristics of cancerous lesions:
1. Single lesion
2. Hard
3. Immovable
4. Irregular borders
5. Size >2 cm
E. Clinical evaluation of breast lumps:
1. Lump contour. Smooth, well-demarcated
lumps are usually benign.
2. Breast pain. Although usually painless, breast
cancer can be accompanied by pain.
3. Nipple discharge. Discharge is uncommon in
cancer and, if present, is unilateral.
4. Lymph node examination. Careful examina-
tion of the axillae and supraclavicular area.
F. Clinical follow-up. In women under the age of 35
years who present with a breast lump with no
suspicious physical findings, it is sometimes ad-
vised that the patient return three to ten days after
the onset of the next menstruation.
 Risk Factors for Developing Breast Cancer

Risk factors Low High Rela-

risk risk tive
risk

Deleterious Nega- Posi- 3-7

BRCA1/BRCA2 tive tive
genes 2.6
Mother or sister with No Yes
breast cancer 18.0
Age 30 to 70 to 1.5
Age at menarche 34 74 1.9-
Age at first birth >14 <12 3.5
Age at menopause <20 >30 2.0
Use of contraceptive <45 >55 1.2
pills Never Past/c
urrent 1.4
Hormone replace- Never use
ment therapy Cur- 1.4
Alcohol None rent
1.8-6
Breast density on 0 2 to 5
mammography (%) drinks/ 2.7-
Bone density Lowest day 3.5
quartile >75
History of a benign No 1.7
breast biopsy High-
History of atypical No est 3.7
hyperplasia on bi- quartil
opsy e
Yes

Yes

1. Diagnostic mammography is part of the eval-

uation of woman age 35 or older who has a
breast mass to search for other lesions and to
evaluate the mass. Certain mammographic
features suggest malignancy:
a. Increased density
b. Irregular margins
c. Spiculation
d. Clustered irregular microcalcifications
2. Mammography usually cannot determine
whether a lump is benign. The sensitivity and
specificity of diagnostic mammography in
women not reporting a breast lump is 82.3 and
91.2% respectively; in women with a self-re-
ported breast lump, the sensitivity and specific-
ity is 87.3 and 84.5%, respectively.
3. Mammography misses 10 to 20% of clinically
palpable breast cancers. Thus, a negative
mammogram should not stop further investiga-
tion if a suspicious lump is felt.
4. Diagnostic mammography is not ordered rou-
tinely in women under age 35. The breast tis-
sue in younger women is often too dense to
evaluate the lump.
G. Ultrasonography can determine whether a breast
mass is a simple or complex cyst or a solid tumor.
It is most useful in the following:
1. Women under age 35
2. Evaluation of a non-palpable mass detected on
screening mammography
3. Patient declining aspiration of a mass
4. Mass that is too small or deep for aspiration
H. The risk of cancer is low if the lesion is a simple
cyst on ultrasound.
I. The negative predictive value of ultrasound in the
patient with a palpable breast mass and a non-
suspicious mammogram is over 97%.
J. Fine needle aspiration biopsy (FNAB) can be
useful in determining if a palpable lump is a sim-
ple cyst. The mass is stabilized between the fin-
gers of one hand, and a 22 to 24-gauge needle is
inserted. Local anesthesia may be used, but is not
always required.
1. FNAB is especially valuable in evaluating cystic
breast lesions and can be therapeutic if all of
the fluid is removed. There are three possible
sample findings with FNAB:
a. Non-bloody fluid. Fluid that is obtained and
is not bloody does not need to be sent for
analysis. The mass should disappear with
the removal of fluid and the patient can be
reassured and checked in four to six weeks
to ensure that the cyst has not reappeared;
recurrence suggests the need for surgical
referral.
b. Bloody fluid from patients with otherwise
benign examinations should be sent for
pathological analysis; cancer is found in 7%
of such cases The patient should be
checked in four to six weeks to ensure that
the cyst has not reappeared. If cytologic ex-
amination is suspicious, or if there is a resid-
ual mass after aspiration, the patient should
be referred to a breast surgeon.
c. No fluid. When no fluid is obtained and the
mass turns out to be solid, cells can be ob-
tained for cytologic analysis with FNAB by
aspirating cells from the solid mass.
2. Core needle biopsy. Core needle biopsy uses
a larger needle (14 to 18 gauge, compared with
22 to 24 gauge), and thereby provides
histologic material. Core needle biopsies are
often performed using stereotactic
mammographic equipment or ultrasound guid-
ance.
K. Triple diagnosis refers to the use of physical
examination, mammography, and FNAB for diag-
nosing palpable breast lumps. Very few breast
cancers are missed using triple diagnosis. Rec-
ommendations for follow-up with the triple diagno-
sis approach are:
1. Women in whom all three tests suggest benign
disease are followed with physical examination
every three to six months for one year to make
sure the mass is stable or regresses.
2. Women in whom all three tests suggest malig-
nancy are referred for definitive therapy.
3. Women with any one of the tests suggesting
malignancy undergo excisional biopsy.
II. Guidelines for breast lump evaluation
A. Women age 35 and older
1. If the initial physical examination does not con-
firm the presence of a dominant mass, a follow-
up examination in 2 to 3 months should be
completed. Women who have not had a
mammogram in the preceding year and are
eligible for regular screening, should have a
mammogram.
2. Women with a dominant mass should undergo
either ultrasonography or a fine needle aspira-
tion biopsy (FNAB). Diagnostic mammography
should be obtained if ultrasound or FNAB re-
sults suggest the lesion is not a simple cyst.
3. Ultrasound should be obtained for palpable
lumps that do not feel cystic. If ultrasound dem-
onstrates a solid mass, the patient should un-
dergo definitive diagnosis with FNAB, core
needle biopsy, or excisional biopsy.
4. Ultrasound or FNAB should be performed for
lumps that feel cystic.
5. If ultrasound demonstrates a simple cyst, no
invasive evaluation is indicated. If a complex
cyst or solid mass is present on ultrasound, the
patient should undergo definitive diagnosis with
FNAB, core needle biopsy, or excisional bi-
opsy.
6. If FNAB is performed first and yields clear fluid
and the mass disappears, the patient can be
reassured and followed in four to six weeks to
check for recurrence or reaccumulation. Recur-
rence requires surgical referral. Bloody fluid
should be sent for cytology.
7. If fluid is not obtained, cellular material should
be sent for cytology. If the sample does not
contain adequate material, the patient should
be sent for surgical evaluation.
8. If cellular material is obtained that is atypical or
suspicious for cancer, the patient should be
referred for a core-needle biopsy or excisional
biopsy.
B. Women younger than age 35
1. Evaluation of a breast mass in a young woman
should follow the procedure recommended for
women age 35 and older, with the following
exceptions:
a. If a dominant mass is found but is not suspi-
cious for cancer, the patient may be asked
to return three to ten days after the next
menstruation for reevaluation. Further inves-
tigation is indicated if the lump remains pal-
pable.
b. Diagnostic mammography should not be
performed in the initial evaluation of women
under age 35.

Benign Breast Disease

Benign breast disease includes breast pain, breast
lumps, or nipple discharge. The most common cause of
breast nodularity and tenderness is fibrocystic change,
which occurs in 60% of premenopausal women.
I. Benign breast lesions, which are discovered by
breast palpation or mammography, have been subdi-
vided into those that are associated with an increased
risk of breast cancer and those that are not.
A. No increased risk of breast cancer
1. Fibrocystic changes consist of an increased
number of cysts or fibrous tissue in an other-
wise normal breast. Fibrocystic changes do not
constitute a disease state.
2. Fibrocystic disease is diagnosed when
fibrocystic changes occur in conjunction with
pain, nipple discharge, or a degree of lumpi-
ness sufficient to cause suspicion of cancer.
3. Duct ectasia is characterized by distention of
subareolar ducts.
4. Solitary papillomas consist of papillary cells
that grow from the wall of a cyst into its lumen.
5. Simple fibroadenomas are benign solid tu-
mors, usually presenting as a well-defined,
mobile mass.
B. Increased risk of breast cancer
1. Ductal hyperplasia without atypia is the most
common lesion associated with increased risk
of breast cancer.
2. Sclerosing adenosis consists of lobular tissue
that has undergone hyperplastic change.
3. Diffuse papillomatosis refers to the formation
of multiple papillomas.
4. Complex fibroadenomas are tumors that con-
tain cysts >3 mm in diameter, sclerosing
adenosis, epithelial calcification, or papillary
apocrine changes.
5. Atypical hyperplasia is associated with a four
to sixfold increased risk of breast cancer.
6. Radial scars are benign breast lesions of un-
certain pathogenesis that are occasionally de-
tected by mammography. Thus, histologic con-
firmation is required to exclude spiculated car-
cinoma.
II. Symptoms and signs of benign breast disease
A. Women with fibrocystic changes can have breast
tenderness during the luteal phase of the men-
strual cycle. Fibrocystic disease is characterized
by more severe or prolonged pain.
B. Women in their 30s sometimes present with multi-
ple breast nodules 2 to 10 mm in size as a result
of proliferation of glandular cells.
C. Women in their 30s and 40s present with solitary
or multiple cysts. Acute enlargement of cysts may
cause severe, localized pain of sudden onset.
Nipple discharge is common, varying from pale
green to brown.
III. Differential diagnosis
A. Breast pain
1. Women with mastitis usually complain of the
sudden onset of pain,fever, erythema, tender-
ness, and induration.
2. Large pendulous breasts may cause pain due
to stretching of Cooper's ligaments.
3. Hidradenitis suppurativa can present as breast
nodules and pain.
4. Chest wall pain induced by trauma or trauma-
induced fat necrosis, intercostal neuralgia,
costochondritis, underlying pleuritic lesions, or
arthritis of the thoracic spine can mimic benign
breast disease.
B. Nipple discharge is uncommon in cancer and, if
present, is unilateral. Approximately 3% of cases
of unilateral nipple discharge are due to breast
cancer; a mass is usually also present.
1. Nonspontaneous, nonbloody, or bilateral nipple
discharge is unlikely to be due to cancer.
a. Purulent discharge is often caused by masti-
tis or a breast abscess.
b. Milky discharge commonly occurs after child-
bearing and can last several years; it also
may be associated with oral contraceptives
or tricyclic antidepressants. Serum prolactin
should be measured if the discharge is sus-
tained, particularly if it is associated with
menstrual abnormalities.
c. A green, yellow, white, grey, or brown dis-
charge can be caused by duct ectasia.
2. Evaluation of nipple discharge for suspected
cancer may include cytology and
galactography. Occult blood can be detected
with a guaiac test.
IV. Clinical evaluation
A. History
 1. The relationship of symptoms to the menstrual
cycles, the timing of onset of breast lumps and
their subsequent course, the color and location
of nipple discharge, and hormone use should
be assessed.
2. Risk factors for breast cancer should be deter-
mined, including menarche before age 12
years, first live birth at age >30 years, and
menopause at age >55 years; the number of
previous breast biopsies, the presence of atypi-
cal ductal hyperplasia on biopsy, obesity,
nulliparity, increased age, the amount of alco-
hol consumed, and the number and ages of
first-degree family members with breast cancer
with two such relatives with breast cancer at
any early age should be determined.
B. Physical examination. The examination is per-
formed when the breasts are least stimulated,
seven to nine days after the onset of menses. The
four breast quadrants, subareolar areas, and the
axillae should be systematically examined with the
woman both lying and sitting with her hands on
her hips.
1. The specific goals of the examination are
to:
a. Delineate and document breast masses
b. Elicit discharge from a nipple
c. Identify localized areas of tenderness
d. Detect enlarged axillary or supraclavicular
lymph nodes
e. Detect skin changes, noting the symmetry
and contour of the breasts, position of the
nipples, scars, dimpling, edema or ery-
thema, ulceration or crusting of the nipple
2. "Classic" characteristics of breast cancers:
a. Single lesion
b. Hard
c. Immovable
d. Irregular border
e. Size >2 cm
C. Mammography
1. Although 90% or more of palpable breast
masses in women in their 20s to early 50s are
benign, excluding breast cancer is a crucial
step in the evaluation. Mammography is recom-
mended for any woman age 35 years or older
who has a breast mass.
2. Mammography usually is not ordered routinely
in women under age 35 years. The breast tis-
sue in younger women is often too dense to
evaluate the lump. Ultrasonography is useful in
these women to evaluate lumps and to assess
for cysts.
3. Round dense lesions on mammography often
represent cystic fluid. Solid and cystic lesions
can often be distinguished by ultrasonography
and mammography, and needle aspiration
under ultrasound guidance further documents
the cystic nature of the lesion.
D. Breast pain. Women who present with breast
pain as their only symptom often undergo mam-
mography. Only 0.4% of women with breast pain
have breast cancer. The vast majority of women
have normal findings (87%); benign abnormalities
are noted in 9%.
E. Ductal lavage. The cytologic detection of cellular
atypia can identify women with a higher risk of
developing breast cancer.
V. Treatment
A. Fibrocystic disease. The major aim of therapy in
fibrocystic disease is to relieve breast pain or
discomfort. Symptomatic relief also may be
achieved with a soft brassiere with good support,
acetaminophen or a nonsteroidal anti-inflamma-
tory drug, or both.
1. Breast pain or discomfort may be relieved with
a thiazide diuretic.
2. Avoidance of caffeine may provide some pa-
tients with relief of pain.
3. Vitamin E, 400 IU twice daily reduces breast
pain.
4. Evening primrose oil in doses of 1500-3000
mg daily, relieves breast pain in 30 to 80%.
5. Danazol in doses of 100 to 200 mg daily re-
duces breast pain. Common side effects in-
clude weight gain, acne, hirsutism, bloating,
and amenorrhea.
6. Tamoxifen reduces breast pain in about 70%
of women. It is safe and well-tolerated as 10
mg twice daily, or bromocriptine 1.25 to 5 mg
daily can be tried.
7. Oral contraceptives. The frequency of
fibrocystic changes decreases with prolonged
oral contraceptive therapy. Oral contraceptives
containing 19-norprogestins, such as norlutate,
have androgenic properties that are beneficial.
References: See page 208.

Sexual Assault
Sexual assault is defined as any sexual act performed
by one person on another without the person's consent.
Sexual assault includes genital, anal, or oral penetration
by a part of the accused's body or by an object. It may
result from force, the threat of force, or the victim's in-
ability to give consent. The annual incidence of sexual
assault is 200 per 100,000 persons.

I. Psychological effects
A. A woman who is sexually assaulted loses control
over her life during the period of the assault. Her
integrity and her life are threatened. She may ex-
perience intense anxiety, anger, or fear. After the
assault, a "rape-trauma" syndrome often occurs.
The immediate response may last for hours or
days and is characterized by generalized pain,
headache, chronic pelvic pain, eating and sleep
disturbances, vaginal symptoms, depression, anxi-
ety, and mood swings.
B. The delayed phase is characterized by flashbacks,
nightmares, and phobias.
II. Medical evaluation
A. Informed consent must be obtained before the
examination. Acute injuries should be stabilized.
About 1% of injuries require hospitalization and
major operative repair, and 0.1% of injuries are
fatal.
B. A history and physical examination should be per-
formed. A chaperon should be present during the
history and physical examination to reassure the
victim and provide support. The patient should be
asked to state in her own words what happened,
identify her attacker if possible, and provide details
of the act(s) performed if possible.

Clinical Care of the Sexual Assault Victim

Medical
Obtain informed consent from the patient
Obtain a gynecologic history
Assess and treat physical injuries
Obtain appropriate cultures and treat any existing
infections
Provide prophylactic antibiotic therapy and offer
immunizations
Provide therapy to prevent unwanted conception
Offer baseline serologic tests for hepatitis B virus,
human immunodeficiency virus (HIV), and syphilis
Provide counseling
Arrange for follow-up medical care and counseling

Legal
Provide accurate recording of events
Document injuries
Collect samples (pubic hair, fingernail scrapings,
vaginal secretions, saliva, blood-stained clothing)
Report to authorities as required
Assure chain of evidence

C. Previous obstetric and gynecologic conditions

should be sought, particularly infections, preg-
nancy, use of contraception, and date of the last
menstrual period. Preexisting pregnancy, risk for
pregnancy, and the possibility of preexisting infec-
tions should be assessed.
D. Physical examination of the entire body and
photographs or drawings of the injured areas
should be completed. Bruises, abrasions, and
lacerations should be sought. Superficial or exten-
sive lacerations of the hymen and vagina, injury to
the urethra, and occasionally rupture of the vaginal
vault into the abdominal cavity may be noted. Bite
marks are common.
1. Pelvic examination should assess the status
of the reproductive organs, collect samples
from the cervix and vagina, and test for
Neisseria gonorrhoeae and Chlamydia
trachomatis.
2. A Wood light should be used to find semen on
the patient's body: dried semen will fluoresce.
Sperm and other Y-chromosome-bearing cells
may be identified from materials collected from
victims.
E. A serum sample should be obtained for baseline
serology for syphilis, herpes simplex virus, hepati-
tis B virus, and HIV.
F. Trichomonas is the most frequently acquired
STD. The risk of acquiring human immunodefi-
ciency virus (HIV) <1% during a single act of het-
erosexual intercourse, but the risk depends on the
population involved and the sexual acts per-
formed. The risk of acquiring gonorrhea is 6-12%,
and the risk of acquiring syphilis is 3%.
G. Hepatitis B virus is 20 times more infectious than
HIV during sexual intercourse. Hepatitis B immune
globulin (0.06 mL of hepatitis B immune globulin
per kilogram) should be administered intramuscu-
larly as soon as possible within 14 days of expo-
sure. It is followed by the standard three-dose
immunization series with hepatitis B vaccine (0, 1,
and 6 months), beginning at the time of hepatitis B
immune globulin administration.
H. Emergency contraception. If the patient is found
to be at risk for pregnancy as a result of the as-
sault, emergency contraception should be offered.
The risk of pregnancy after sexual assault is 2-4%
in victims not already using contraception. One
dose of combination oral contraceptive tablets is
given at the time the victim is seen and an addi-
tional dose is given in 12 hours. Emergency con-
traception can be effective up to 120 hours after
unprotected coitus. Metoclopramide (Reglan), 20
mg with each dose of hormone, is prescribed for
nausea. A pregnancy test should be performed at
the 2-week return visit if conception is suspected.

Emergency Contraception

1. Consider pretreatment one hour before each oral contra-

ceptive pill dose, using one of the following orally admin-
istered antiemetic agents:
Prochlorperazine (Compazine), 5 to 10 mg
Promethazine (Phenergan), 12.5 to 25 mg
Trimethobenzamide (Tigan), 250 mg
2. Administer the first dose of oral contraceptive pill within
72 hours of intercourse, and administer the second dose
12 hours after the first dose. Brand name options for
emergency contraception include the following:
Preven Kit--two pills per dose (0.5 mg of levonorgestrel
and 100 µg of ethinyl estradiol per dose)
Ovral--two pills per dose (0.5 mg of levonorgestrel and
100 µg of ethinyl estradiol per dose)
Plan B--one pill per dose (0.75 mg of levonorgestrel per
dose)
Nordette--four pills per dose (0.6 mg of levonorgestrel
and 120 µg of ethinyl estradiol per dose)
Triphasil--four pills per dose (0.5 mg of levonorgestrel
and 120 µg of ethinyl estradiol per dose)

Screening and Treatment of Sexually Transmissi-

ble Infections Following Sexual Assault

Initial Examination

Infection
• Testing for and gonorrhea and chlamydia from specimens
from any sites of penetration or attempted penetration
• Wet mount and culture or a vaginal swab specimen for
Trichomonas
• Serum sample for syphilis, herpes simplex virus, hepatitis
B virus, and HIV
Pregnancy Prevention
Prophylaxis
• Hepatitis B virus vaccination and hepatitis B immune
globulin.
• Empiric recommended antimicrobial therapy for
chlamydial, gonococcal, and trichomonal infections and
for bacterial vaginosis:
Ceftriaxone, 125 mg intramuscularly in a single dose, plus
Metronidazole, 2 g orally in a single dose, plus
Doxycycline 100 mg orally two times a day for 7 days
Azithromycin (Zithromax) is used if the patient is unlikely
to comply with the 7 day course of doxycycline; single
dose of four 250 mg caps.
If the patient is penicillin-allergic, ciprofloxacin 500 mg PO
or ofloxacin 400 mg PO is substituted for ceftriaxone. If
the patient is pregnant, erythromycin 500 mg PO qid for
7 days is substituted for doxycycline.
HIV prophylaxis consists of zidovudine (AZT) 200 mg PO
tid, plus lamivudine (3TC) 150 mg PO bid for 4 weeks.
 Follow-Up Examination (2 weeks)

• Cultures for N gonorrhoeae and C trachomatis (not

needed if prophylactic treatment has been provided)
• Wet mount and culture for T vaginalis
• Collection of serum sample for subsequent serologic
analysis if test results are positive

Follow-Up Examination (12 weeks)

Serologic tests for infectious agents:

T pallidum
HIV (repeat test at 6 months)
Hepatitis B virus (not needed if hepatitis B virus vaccine
was given)

III. Emotional care

A. The physician should discuss the injuries and the
probability of infection or pregnancy with the vic-
tim, and she should be allowed to express her
anxieties.
B. Anxiolytic medication may be useful; lorazepam
(Ativan) 1-5 mg PO tid prn anxiety.
C. The patient should be referred to personnel
trained to handle rape-trauma victims within 1
week.
IV. Follow-up care
A. The patient is seen for medical follow-up in 2
weeks for documentation of healing of injuries.
B. Repeat testing includes syphilis, hepatitis B, and
gonorrhea and chlamydia cultures. HIV serology
should be repeated in 3 months and 6 months.
C. A pregnancy test should be performed if concep-
tion is suspected.
References: See page 208.

Osteoporosis
Over 1.3 million osteoporotic fractures occur each year
in the United States. The risk of all fractures increases
with age; among persons who survive until age 90, 33%
of women will have a hip fracture. The lifetime risk of hip
fracture for white women at age 50 is 16%. Osteoporosis
is characterized by low bone mass, microarchitectural
disruption, and increased skeletal fragility.

Risk Factors for Osteoporotic Fractures

Personal history of fracture White race

as an adult
History of fracture in a first-
degree relative
Current cigarette smoking
Low body weight (less than
58 kg [127 lb])
Female sex
Estrogen deficiency (meno-
pause before age 45 years
or bilateral ovariectomy,
prolonged premenopausal
amenorrhea [>one year])
Advanced age
Lifelong low calcium intake
Alcoholism
Inadequate physical activity
Recurrent falls
Dementia
Impaired eyesight despite
adequate correction
Poor health/frailty

I. Screening for osteoporosis and osteopenia

A. Normal bone density is defined as a bone mineral
density (BMD) value within one standard deviation
of the mean value in young adults of the same sex
and race.
B. Osteopenia is defined as a BMD between 1 and
2.5 standard deviations below the mean.
C. Osteoporosis is defined as a value more than 2.5
standard deviations below the mean; this level is
the fracture threshold. These values are referred to
as T-scores (number of standard deviations above
or below the mean value).
D. Dual x-ray absorptiometry. In dual x-ray
absorptiometry (DXA), two photons are emitted
from an x-ray tube. DXA is the most commonly
used method for measuring bone density because
it gives very precise measurements with minimal
radiation. DXA measurements of the spine and hip
are recommended.
II. Recommendations for screening for osteoporosis
of the National Osteoporosis Foundation
A. All women should be counseled about the risk
factors for osteoporosis, especially smoking cessa-
tion and limiting alcohol. All women should be
encouraged to participate in regular weight-bear-
ing and exercise.
B. Measurement of BMD is recommended for all
women 65 years and older regardless of risk fac-
tors. BMD should also be measured in all women
under the age of 65 years who have one or more
risk factors for osteoporosis (in addition to meno-
pause). The hip is the recommended site of mea-
surement.
C. All adults should be advised to consume at least
1,200 mg of calcium per day and 400 to 800 IU of
vitamin D per day. A daily multivitamin (which pro-
vides 400 IU) is recommended. In patients with
documented vitamin D deficiency, osteoporosis, or
previous fracture, two multivitamins may be rea-
sonable, particularly if dietary intake is inadequate
and access to sunlight is poor.
D. Treatment is recommended for women without risk
factors who have a BMD that is 2 SD below the
mean for young women, and in women with risk
factors who have a BMD that is 1.5 SD below the
mean.
III. Nonpharmacologic therapy of osteoporosis in
women
A. Diet. An optimal diet for treatment (or prevention)
of osteoporosis includes an adequate intake of
calories (to avoid malnutrition), calcium, and vita-
min D.
B. Calcium. Postmenopausal women should be ad-
vised to take 1000 to 1500 mg/day of elemental
calcium, in divided doses, with meals.
C. Vitamin D total of 800 IU daily should be taken.
D. Exercise. Women should exercise for at least 30
minutes three times per week. Any weight-bearing
exercise regimen, including walking, is acceptable.
E. Cessation of smoking is recommended for all
women because smoking cigarettes accelerates
bone loss.
IV. Drug therapy of osteoporosis in women
A. Selected postmenopausal women with osteoporo-
sis or at high risk for the disease should be consid-
ered for drug therapy. Particular attention should
be paid to treating women with a recent fragility
fracture, including hip fracture, because they are at
high risk for a second fracture.
B. Candidates for drug therapy are women who al-
ready have postmenopausal osteoporosis (less
than -2.5) and women with osteopenia (T score -1
to -2.5) soon after menopause.
C. Bisphosphonates
1. Alendronate (Fosamax) (10 mg/day or 70 mg
once weekly) or risedronate (Actonel) (5
mg/day or 35 mg once weekly) are good choices
for the treatment of osteoporosis.
Bisphosphonate therapy increases bone mass
and reduces the incidence of vertebral and
nonvertebral fractures.
2. Alendronate (5 mg/day or 35 mg once weekly)
and risedronate (5 mg/day of 35 mg once
weekly) have been approved for prevention of
osteoporosis.
3. Alendronate or risedronate should be taken with
a full glass of water 30 minutes before the first
meal or beverage of the day. Patients should
not lie down for at least 30 minutes after taking
the dose to avoid the unusual complication of
pill-induced esophagitis.
4. Alendronate is well tolerated and effective for at
least seven years.
5. The bisphosphonates (alendronate or
risedronate) and raloxifene are first-line treat-
ments for prevention of osteoporosis. The
bisphosphonates are first-line therapy for treat-
ment of osteoporosis. Bisphosphonates are
preferred for prevention and treatment of osteo-
porosis because they increase bone mineral
density more than raloxifene.
D. Selective estrogen receptor modulators
1. Raloxifene (Evista) (5 mg daily or a once-a-
week preparation) is a selective estrogen recep-
tor modulator (SERM) for prevention and treat-
ment of osteoporosis. It increases bone mineral
density and reduces serum total and low-
density-lipoprotein (LDL) cholesterol. It also
appears to reduce the incidence of vertebral
fractures and is one of the first-line drugs for
prevention of osteoporosis.
2. Raloxifene is somewhat less effective than the
bisphosphonates for the prevention and treat-
ment of osteoporosis. Venous thrombo-
embolism is a risk.

Treatment Guidelines for Osteoporosis

Calcium supplements with or without vitamin D supplements

or calcium-rich diet
Weight-bearing exercise
Avoidance of alcohol tobacco products
Alendronate (Fosamax)
Risedronate (Actonel)
Raloxifene (Evista)

Agents for Treating Osteoporosis

Medication Dosage Route

Calcium 1,000 to 1,500 mg per day Oral

Vitamin D 400 IU per day (800 IU per Oral

day in winter in northern lati-
tudes)

Alendronate Prevention: 5 mg per day or Oral

(Fosamax) 35 mg once-a-week
Treatment: 10 mg per day or
70 mg once-a-week

Risedronate 5 mg daily or 35 mg once Oral

(Actonel) weekly

Raloxifene 60 mg per day Oral

(Evista)

E. Monitoring the response to therapy

1. Bone mineral density and a marker of bone
turnover should be measured at baseline, fol-
lowed by a repeat measurement of the marker
in three months.
2. If the marker falls appropriately, the drug is hav-
ing the desired effect, and therapy should be
continued for two years, at which time bone
mineral density can be measured again. The
anticipated three-month decline in markers is
50% with alendronate.
F. Estrogen/progestin therapy
1. Estrogen-progestin therapy is no longer a first-
line approach for the treatment of osteoporosis
in postmenopausal women because of in-
creases in the risk of breast cancer, stroke,
venous thromboembolism, and coronary dis-
ease.
2. Indications for estrogen-progestin in
postmenopausal women include persistent
menopausal symptoms and patients with an
indication for antiresorptive therapy who cannot
tolerate the other drugs.
References: See page 208.

Infertility
Infertility is defined as failure of a couple of reproductive
age to conceive after 12 months or more of regular
coitus without using contraception. Infertility is consid-
ered primary when it occurs in a woman who has never
established a pregnancy and secondary when it occurs
in a woman who has a history of one or more previous
pregnancies. Fecundability is defined as the probability
of achieving a pregnancy within one menstrual cycle. It
is estimated that 10% to 20% of couples are infertile.

I. Diagnostic evaluation
A. History
1. The history should include the couple's ages,
the duration of infertility, previous infertility in
other relationships, frequency of coitus, and use
of lubricants (which can be spermicidal).
Mumps orchitis, renal disease, radiation ther-
apy, sexually transmitted diseases, chronic
disease such as tuberculosis, major stress and
fatigue, or a recent history of acute viral or fe-
brile illness should be sought. Exposure to radi-
ation, chemicals, excessive heat from saunas
or hot tubs should be investigated.
2. Pelvic inflammatory disease, previous pregnan-
cies, douching practices, work exposures, alco-
hol and drug use, exercise, and history of any
eating disorders should be evaluated.
3. Menstrual cycle length and regularity and indi-
rect indicators of ovulation, such as
Mittelschmerz, mid-cycle cervical mucus
change and premenstrual molimina, should be
assessed.
B. Physical examination for the woman
1. Vital signs, height, and weight should be noted.
Hypertension hair distribution, acne, hirsutism,
thyromegaly, enlarged lymph nodes, abdominal
masses or scars, galactorrhea, or acanthosis
nigricans (suggestive of diabetes) should be
sought.
 2. Pelvic examination should include a
Papanicolaou smear and bimanual examination
to assess uterine size and any ovarian masses.
3. Testing for Chlamydia trachomatis,
Mycoplasma hominis, and Ureaplasma
urealyticum are recommended.
C. Physical examination for the man
1. Height, weight, and hair distribution,
gynecomastia, palpable lymph nodes or
thyromegaly should be sought.
2. The consistency, size, and position of both tes-
ticles and the presence of varicocele or abnor-
mal location of the urethral meatus on the penis
should be noted. Testing for Chlamydia,
Ureaplasma, and Mycoplasma should be com-
pleted.
D. The cornerstone of any infertility evaluation relies
on the assessment of six basic elements: (1) se-
men analysis, (2) sperm-cervical mucus interac-
tion, (3) ovulation, (4) tubal patency, and (5) uter-
ine and (6) peritoneal abnormalities. Couples of
reproductive age who have intercourse regularly
without contraception have approximately a 25-
30% chance of conceiving in a given menstrual
cycle and an 85% chance of conceiving within 1
year.
E. Semen analysis. The specimen is routinely ob-
tained by masturbation and collected in a clean
glass or plastic container. It is customary to have
the man abstain from ejaculation for at least 2
days before producing the specimen. Criteria for a
normal semen analysis include a sperm count >20
million sperm/mL with at least 50% motility and
30% normal morphology.

Semen Analysis Interpretation

Semen Pa- Normal Val- Poor Progno-

rameter ues sis

Sperm concen- >20 x 106/mL <5 million/ mL

tration

Sperm motility >50% progres- <10% motility

sive motility

Sperm morphol- >50% normal <4% normal

ogy

Ejaculate volume >2 cc <2 cc

F. The postcoital test (PCT) is used to assess sperm-

cervical mucus interaction after intercourse. The
PCT provides information regarding cervical mu-
cus quality and survivability of sperm after inter-
course. The PCT should be performed 8 hours
after intercourse and 1 to 2 days before the pre-
dicted time of ovulation, when there is maximum
estrogen secretion unopposed by progesterone.
G. Ovulation assessment
1. Commonly used methods used to assess ovu-
lation include measuring a rise in basal body
temperature (BBT), identifying an elevation in
the midluteal phase serum progesterone con-
centration, luteal phase endometrial biopsy,
and detection of luteinizing hormone (LH) in the
urine. The BBT chart is used to acquire infor-
mation regarding ovulation and the duration of
the luteal phase. Female patients are instructed
to take their temperature upon awaking each
morning before any physical activity. A temper-
ature rise of 0.4EF (0.22EC) for 2 consecutive
days is indicative of ovulation. The initial rise in
serum progesterone level occurs between 48
hours before ovulation and 24 hours after ovu-
lation. For this reason, a rise in temperature is
useful in establishing that ovulation has oc-
curred, but it should not be used to predict the
onset of ovulation in a given cycle.
2. Another test used to assess ovulation is a
midluteal phase serum progesterone concen-
tration. A blood sample is usually obtained for
progesterone 7 days after the estimated day of
ovulation. A concentration >3.0 ng/mL is con-
sistent with ovulation, while a concentration >10
ng/mL signifies adequate luteal phase support.
3. Alternatively, urine LH kits can be used to as-
sess ovulation. Unlike the rise in BBT and se-
rum progesterone concentrations, which are
useful for retrospectively documenting ovula-
tion, urinary LH kits can be used to predict ovu-
lation. Ovulation usually occurs 24 to 36 hours
after detecting the LH surge.
H. Tubal patency can be evaluated by
hysterosalpingography (HSG) and/or by
chromopertubation during laparoscopy.

Timing of the Infertility Evaluation

Test Day

Hysterosalpingogram day 7-10

Postcoital Test day 12-14

Serum Progesterone day 21-23

Endometrial Biopsy day 25-28

II. Differential diagnosis and treatment

A. The differential diagnosis of infertility includes
ovarian (20%), pelvic (25%), cervical (10%), and
male (35%) factors. In approximately 10% of cases
no explanation is found. Optimal frequency of co-
itus is every other day around the time of ovulation;
however, comparable pregnancy rates are
achieved by 3-4 times weekly intercourse through-
out the cycle.
B. Ovarian factor infertility
1. An ovarian factor is suggested by irregular cy-
cles, abnormal BBT charts, midluteal phase
serum progesterone levels less than 3 ng/mL,
or luteal phase defect documented by
endometrial biopsy. Ovulatory dysfunction may
be intrinsic to the ovaries or caused by thyroid,
adrenal, prolactin, or central nervous system
disorders. Emotional stress, changes in weight,
or excessive exercise should be sought be-
cause these disorders can result in ovulatory
dysfunction. Luteal phase deficiency is most
often the result of inadequate ovarian proges-
terone secretion.
2. Clomiphene citrate (Clomid, CC) is the most
cost-effective treatment tor the treatment of
infertility related to anovulation or oligo ovula-
tion. The usual starting dose of CC is 50 mg/day
for 5 days, beginning on the second to sixth day
after induced or spontaneous bleeding. Ovula-
tion is expected between 7 and 10 days after
the last dose of CC.
3. Ovulation on a specified dosage of CC should
be confirmed with a midluteal phase serum
progesterone assay, BBT rise, pelvic
ultrasonography, or urinary ovulation-predictor
kits. In the event ovulation does not occur with a
specified dose of CC, the dose can be in-
creased by 50 mg/day in a subsequent cycle.
The maximum dose of CC should not exceed
250 mg/day. The addition of dexamethasone is
advocated for women with elevated
dehydroepiandrosterone sulfate levels who
remain anovulatory despite high doses of CC.
The incidence of multiple gestations with CC is
5% to 10%. Approximately 33% of patients will
become pregnant within five cycles of treatment.
Treatment with CC for more than six ovulatory
cycles is not recommended because of low
success rates.
4. Human menopausal gonadotropins (hMG,
Pergonal, Metrodin) ovulation induction with is
another option for the treatment of ovulatory
dysfunction. Because of its expense and associ-
ated risk of multiple gestations, gonadotropin
therapy should be reserved for patients who
remain refractory to CC therapy. The pregnancy
rate with gonadotropin therapy is 25% per cycle.
This is most likely the result of recruitment of
more follicles with gonadotropin therapy. The
incidence of multiple gestations with gonadotro-
pin therapy is 25% to 30%.
5. Luteal phase deficiency is treated with pro-
gesterone, usually prescribed as an intravaginal
suppository at a dose of 25 mg twice a day until
8 to 10 weeks of gestation.
6. Women with ovulatory dysfunction second-
ary to ovarian failure or poor ovarian reserve
should consider obtaining oocytes from a donor
source.
C. Pelvic factor infertility
1. Pelvic factor infertility is caused by conditions
that affect the fallopian tubes, peritoneum, or
uterus. Tubal factor infertility is a common
sequela of salpingitis. Appendicitis, ectopic
pregnancy, endometriosis, and previous pelvic
or abdominal surgery can also damage the fal-
lopian tubes and cause adhesion formation.
2. Endometriosis is another condition involving the
peritoneal cavity that is commonly associated
with infertility. Uterine abnormalities are respon-
sible for infertility in about 2% of cases. Exam-
ples of uterine abnormalities associated with
infertility are congenital deformities of the
uterus, leiomyomas, and intrauterine
scarification or adhesions (Asherman's syn-
drome).
3. The mainstay of treatment of pelvic factor infer-
tility relies on laparoscopy and hysteroscopy. In
many instances, tubal reconstructive surgery,
lysis of adhesions, and ablation and resection of
endometriosis can be accomplished
laparoscopically.
D. Cervical factor infertility
1. Cervical factor infertility is suggested when well-
timed PCTs are consistently abnormal in the
presence of a normal semen analysis. Cervical
factor infertility results from inadequate mucus
production by the cervical epithelium, poor mu-
cus quality, or the presence of antisperm anti-
bodies.
2. Patients with an abnormal PCT should be
screened for an infectious etiology. The pres-
ence of immotile sperm or sperm shaking in
place and not demonstrating forward motion is
suggestive of immunologically related infertility.
Sperm-cervical mucus and antisperm antibody
testing are indicated when PCTs are repeatedly
abnormal, despite normal-appearing cervical
mucus and normal semen analysis.
E. Male factor infertility includes conditions that
affect sperm production, sperm maturation, and
sperm delivery. Intrauterine insemination is fre-
quently used to treat men with impaired semen
parameters.
F. Unexplained Infertility
1. The term unexplained infertility should be used
only after a thorough infertility investigation has
failed to reveal an identifiable source and the
duration of infertility is 24 months or more. His-
tory, physical examination, documentation of
ovulation, endometrial biopsy, semen analyses,
PCT, hysterosalpingogram, and laparoscopy
should have been completed.
2. Because couples with unexplained infertility lack
an identifiable causative factor of their infertility,
empirical treatment with clomiphene therapy
increases the spontaneous pregnancy rate to
6.8% per cycle compared with 2.8% in placebo-
control cycles. For optimal results, gonadotro-
pins should be used for ovulation induction.
Intrauterine insemination, in vitro fertilization
and gamete intrafallopian transfer (GIFT) are
additional options.
References: See page 208.

Sexual Dysfunction
Almost two-thirds of the women may have had sexual
difficulties at some time. Fifteen% of women experience
pain with intercourse, 18-48% experience difficulty be-
coming aroused, 46% note difficulty reaching orgasm,
and 15-24% are not orgasmic.

I. Clinical evaluation of sexual dysfunction. Sexual

difficulty can be caused by a lack of communication,
insufficient stimulation, a lack of understanding of
sexual response, lack of nurturing, physical discom-
fort, or fear of infection.
II. Treatment of sexual dysfunction
A. Lack of arousal
1. Difficulty becoming sexually aroused may occur
if there is insufficient foreplay or if either partner
is emotionally distracted. Arousal phase dys-
function may be manifest by insufficient
vasocongestion.
2. Treatment consists of Sensate Focus exercises.
In these exercises, the woman and her partner
take turns caressing each other's body, except
for the genital area. When caressing becomes
pleasurable for both partners, they move on to
manual genital stimulation, and then to further
sexual activity.
 B. Lack of orgasm
1. Lack of orgasm should be considered a prob-
lem if the patient or her partner perceives it as
one. Ninety% of women are able to experience
orgasm.
2. At-home methods of overcoming dysfunc-
tion
a. The patient should increase self-awareness
by examining her body and genitals at home.
The patient should identify sensitive areas
that produce pleasurable feelings. The inten-
sity and duration of psychologic stimulation
may be increased by sexual fantasy.
b. If, after completing the above steps, an or-
gasm has not been reached, the patient may
find that the use of a vibrator on or around
the clitoris is effective.
c. Once masturbation has resulted in orgasm,
the patient should masturbate with her part-
ner present and demonstrate pleasurable
stimulation techniques.
d. Once high levels of arousal have been
achieved, the couple may engage in inter-
course. Manual stimulation of the clitoris
during intercourse may be beneficial.
C. Dyspareunia
1. Dyspareunia consists of pain during inter-
course. Organic disorders that may contribute
to dyspareunia include hypoestrogenism, endo-
metriosis, ovaries located in the cul-de-sac,
fibroids, and pelvic infection.
2. Evaluation for dyspareunia should include care-
ful assessment of the genital tract and an at-
tempt to reproduce symptoms during bimanual
examination.
D. Vaginismus
1. Vaginismus consists of spasm of the levator ani
muscle, making penetration into the vagina
painful. Some women may be unable to un-
dergo pelvic examination.
2. Treatment of vaginismus
a. Vaginal dilators. Plastic syringe covers or
vaginal dilators are available in sets of 4
graduated sizes. The smallest dilator (the
size of the fifth finger) is placed in the vagina
by the woman. As each dilator is replaced
with the next larger size without pain, muscle
relaxation occurs.
b. Muscle awareness exercises
(1) The examiner places one finger inside
the vaginal introitus, and the woman is
instructed to contract the muscle that she
uses to stop urine flow. The woman then
inserts her own finger into the vagina and
contracts. The process is continued at
home.
(2) Once a woman can identify the appropri-
ate muscles, vaginal contractions can be
done without placing a finger in the va-
gina.
E. Medications that interfere with sexual function.
The most common of medications that interfere
with sexual function are antihypertensive agents,
anti-psychotics, and antidepressants.

Medications Associated With Sexual Dysfunction

in Women

Medication Decreased Delayed or No

Libido Orgasm

Amphetamines X
and anorexic
drugs

Cimetidine X

Diazepam X

Fluoxetine X

Imipramine X

Propranolol X

References: See page 208.

Urinary Incontinence
I. Terminology
A. Urinary incontinence is involuntary leakage of
urine.
B. Urgency is the complaint of a sudden and compel-
ling desire to pass urine, that is difficult to defer.
C. Urge incontinence is the complaint of involuntary
leakage accompanied by urgency. Common
precipitants include running water, hand washing,
and exposure to cold.
D. Stress incontinence is involuntary leakage with
effort, exertion, sneezing, or coughing.
E. Mixed incontinence is the complaint of involuntary
leakage associated with urgency and also with
exertion, effort, sneezing, or coughing.
F. Overactive bladder is a symptom syndrome con-
sisting of urgency, frequency, and nocturia, with or
without urge incontinence.
G. Hesitancy describes difficulty in initiating voiding.
H. Straining to void is the muscular effort used either
to initiate, maintain, or improve the urinary stream.
II. Types of urinary incontinence
A. Incontinence related to reversible conditions.
Incontinence affects up to one-third of community-
dwelling older persons and is often caused by
medical and functional factors. Medications often
precipitate or worsen urinary incontinence in older
individuals.
B. Urge incontinence. The etiology of the overactive
bladder syndrome is uninhibited bladder contrac-
tions (called detrusor overactivity).
C. Most common causes of detrusor overactivity:
1. Age-related changes
2. Interruption of central nervous system (CNS)
inhibitory pathways (eg, by stroke, cervical ste-
nosis)
3. Bladder irritation caused by infection, bladder
stones, inflammation, or neoplasms
4. Detrusor overactivity in many cases may be
idiopathic.
5. Urge urinary incontinence in younger women
may be due to interstitial cystitis, characterized
by urgency and frequent voiding of small
amounts of urine, often with dysuria or pain.
D. Urge urinary incontinence in frail older persons
frequently coexists with impaired detrusor contrac-
tile function, a condition termed detrusor hyperac-
tivity with impaired contractility (DHIC). DHIC is
characterized by urgency and an elevated postvoid
residual in the absence of outlet obstruction.
E. Stress incontinence occurs when increases in
intraabdominal pressure overcome sphincter clo-
sure mechanisms. Stress urinary incontinence is
the most common cause of urinary incontinence in
younger women, second most common cause in
older women, and may occur in older men after
transurethral or radical prostatectomy.
1. Causes of stress incontinence:
a. Stress urinary incontinence in women most
often results from impaired urethral support
from pelvic endofascia and muscles.
b. Stress urinary incontinence is less frequently
caused failure of urethral closure, called in-
trinsic sphincter deficiency (ISD). This usually
results from operative trauma and scarring,
but it can also occur with postmenopausal
mucosal atrophy. Unlike the episodic, stress-
maneuver-related leakage of stress urinary
incontinence, ISD leakage typically is contin-
ual.
F. Mixed incontinence is the most common type of
urinary incontinence in women, caused by detrusor
overactivity and impaired urethral sphincter func-
tion.
G. Overflow incontinence is dribbling and/or contin-
uous leakage associated with incomplete bladder
emptying caused by impaired detrusor contractility
and/or bladder outlet obstruction. The postvoid
residual is elevated, and there may be a weak
urinary stream, dribbling, intermittency, hesitancy,
frequency, and nocturia. Stress-related leakage
may occur.
1. Outlet obstruction is the second most common
cause of urinary incontinence in older men (after
detrusor overactivity), resulting from benign
prostatic hyperplasia, prostate cancer, or ure-
thral stricture.
III. Diagnostic evaluation
A. History. The onset and course of incontinence and
associated lower urinary tract symptoms.
B. Leakage frequency, volume, timing, and associ-
ated symptoms (eg, urgency, effort maneuvers,
urinary frequency, nocturia, hesitancy, interrupted
voiding, incomplete emptying, straining to empty,
sense of warning).
C. Precipitants: medications, caffeinated beverages,
alcohol, physical activity, cough, laughing, sound of
water.
D. Bowel and sexual function (impaction can cause
overflow urinary incontinence; bowel control and
sexual function share sacral cord innervation with
voiding).
E. Status of other medical conditions, parity, and
medications, along with their temporal relationship
to urinary incontinence onset.

Key Questions in Evaluating Patients for Urinary

Incontinence

Do you leak urine when you cough, laugh, lift something or

sneeze? How often?
Do you ever leak urine when you have a strong urge on the
way to the bathroom? How often?
How frequently do you empty your bladder during the day?
How many times do you get up to urinate after going to
sleep? Is it the urge to urinate that wakes you?
Do you ever leak urine during sex?
Do you wear pads that protect you from leaking urine? How
often do you have to change them?
Do you ever find urine on your pads or clothes and were
unaware of when the leakage occurred?
Does it hurt when you urinate?
Do you ever feel that you are unable to completely empty
your bladder?

Drugs That Can Influence Bladder Function

Drug Side effect

Antidepressants, Sedation, retention (over-

antipsychotics, seda- flow)
tives/hypnotics

Diuretics Frequency, urgency (OAB)

Caffeine Frequency, urgency (OAB)

Anticholinergics Retention (overflow)

Alcohol Sedation, frequency (OAB)

Narcotics Retention, constipation, se-

dation (OAB and overflow)

Alpha-adrenergic blockers Decreased urethral tone

(stress incontinence)

Alpha-adrenergic agonists Increased urethral tone,

retention (overflow)

Beta-adrenergic agonists Inhibited detrusor function,

retention (overflow)

IV. Physical examination

A. General examination should include the level of
alertness and functional status. Vital signs should
include orthostatic vital signs.
B. Neck examination should investigate limitations
in cervical lateral rotation and lateral flexion,
interosseous muscle wasting, and an abnormal
Babinski reflex. These changes suggest cervical
spondylosis or stenosis, with secondary interrup-
tion of inhibitory tracts to the detrusor, thus caus-
ing detrusor overactivity.
C. Back examination may reveal dimpling or a hair
tuft at the spinal cord base, suggestive of occult
dysraphism (incomplete spina bifida). Evidence
of prior laminectomy should be sought.
D. Cardiovascular examination should look for
evidence of volume overload (eg, rales, pedal
edema).
E. Abdomen should be palpated for masses, ten-
derness, and bladder distention.
F. Extremities should be examined for joint mobility
and function.
G. Genital examination in women should include
inspection of the vaginal mucosa for atrophy
(thinning, pallor, loss of rugae), narrowing of the
introitus by posterior synechia, vault stenosis,
and inflammation (erythema, petechiae,
telangiectasia, friability). A bimanual examination
should be done to evaluate for masses or tender-
ness.
1. The adequacy of pelvic support may be as-
sessed by a split-speculum exam, removing
the top blade of the speculum and holding the
bottom blade firmly against the posterior vagi-
 nal wall. While the woman to coughs, assess
whether the urethra remains firmly fixed or
swings quickly forward (urethral hypermobility)
and for bulging of the anterior vaginal wall
(cystocoele).
2. Check for rectocele by turning the single blade
of the speculum to support the anterior vaginal
wall and having the patient cough again.
3. Uncircumcised men should be checked for
phimosis, paraphimosis, and balanitis.
H. Rectal examination should check for masses
and fecal impaction, and for prostate consistency
and symmetry in men (estimation of prostate size
by digital examination is unreliable).
I. Neurologic examination assess sacral root
integrity, including perineal sensation, resting
and volitional tone of the anal sphincter, anal
wink (anal contraction in response to a light
scratch of the perineal skin lateral to the anus),
and the bulbocavernosus reflex (anal contraction
in response to a light squeeze of the clitoris or
glans penis). Cognitive status and affect should
be assessed, as well as motor strength and tone
(especially with regard to mobility), and vibration
and peripheral sensation for peripheral neuropa-
thy.
J. Clinical testing
1. Stress test is best done when the patient has
not recently voided and is in a standing posi-
tion with a relaxed perineum. The patient
should give a single vigorous cough. A pad is
held underneath the perineum, and the physi-
cian or nurse observes directly whether there
is leakage from the urethra.
a. Leakage instantaneous with cough sug-
gests impaired sphincter function, while a
several-second delay before leakage sug-
gests an effort-induced uninhibited detrusor
contraction.
2. Postvoid residual volume (PVR) by
catheterization or ultrasound. Elevated PVR is
found most commonly in:
a. Frail elderly men with symptoms of bladder
outlet obstruction
b. Patients with symptoms of decreased blad-
der emptying or abdominal distention
c. Women with previous anti-incontinence
surgery
d. Persons with suprasacral and sacral spinal
cord injury
e. Patients who have failed empiric
antimuscarinic drug therapy
f. A PVR of less than 50 mL is considered
adequate emptying, and a PVR >200 mL is
suggestive of either detrusor weakness or
obstruction.
K. Laboratory tests. Renal function tests, glucose,
calcium, and, in older people, a vitamin B12 level
should be obtained. A urinalysis should be per-
formed. Urine cytology and cystoscopy are indi-
cated only if there is hematuria or pelvic pain.
L. Urodynamic testing is not usually necessary in
the evaluation of urinary incontinence.
V. Treatment of urinary incontinence
A. Lifestyle. Adequate fluid intake (up to two liters
per day); avoidance of caffeinated beverages
and alcohol; minimizing evening intake; manage-
ment of constipation; smoking cessation; and
treatment of pulmonary disease if cough is exac-
erbating incontinence.
B. Behavioral therapy
1. Cognitively intact patients
a. Bladder training involves timed voiding
every two hours while awake. Bladder re-
laxation techniques involve having the pa-
tients sit down when an urge occurs and
concentrate on making the urge decrease
and pass by taking a deep breath, contract-
ing their pelvic muscles. Once in control of
the urge, they walk to a bathroom and void.
b. Supplemental biofeedback may be helpful
for some patients in addition to bladder
training.
2. Cognitively impaired patients. Prompted
voiding involves regular monitoring of conti-
nence; prompting to toilet on a scheduled ba-
sis; and praise when individuals are continent
and attempt to toilet.
C. Pelvic muscle (Kegel) exercises (PME)
strengthen the urethral closure mechanism with
small numbers of isometric repetitions at maxi-
mal exertion. The basic recommended regimen
is three sets of 8 to 12 slow velocity contractions
sustained for six to eight seconds each, per-
formed three or four times a week and continued
for at least 15 to 20 weeks.
VI. Pharmacological therapy. Medications are not
useful in the treatment of with stress incontinence.
A. Antimuscarinics. Anticholinergics with
antimuscarinic effects are frequently prescribed
for urge incontinence. These agents result in a
40% higher rate of cure or improvement; dry
mouth is common.
1. Oxybutynin (Ditropan) has direct
antispasmodic effects and inhibits the action
of acetylcholine on smooth muscle.
Oxybutynin is available in both immediate re-
lease (IR), extended release (ER), and trans-
dermal formulations. Efficacy is similar.
a. The initial dosage for IR is 2.5 mg two to
three times daily, followed by titration as
needed up to 20 mg/day in divided doses.
The ER formulation is started at 5 mg once
daily and titrated up to 20 to 30 mg once
daily. The transdermal patch is available at
3.8 mg and should be changed twice a
week.
b. Anticholinergic side effects, especially
dry mouth, can limit therapy; dry mouth is
less frequent with extended release and
transdermal preparations. The postvoid
residual should be monitored in older pa-
tients. Worsening of urinary incontinence
can result from subclinical retention.
2. Tolterodine (Detrol LA, 1 to 2 mg twice a day
immediate release, 2 to 4 mg per day ex-
tended release) has similar efficacy to
oxybutynin. It causes dry mouth less frequently
than oxybutynin IR 5 mg three times daily, but
has similar side effects to ER oxybutynin 10
mg/day. Tolterodine is more expensive than
generic oxybutynin IR. Oxybutynin and
tolterodine have similar clinical efficacy, but
tolterodine causes less dry mouth.
3. Trospium (Sanctura, 20 mg twice daily) is
approved for the treatment of overactive blad-
der. Dose should be reduced to 20 mg once a
day in the elderly and renal impairment.
Trospium must be taken on an empty stom-
ach. Dry mouth occurs in 22% and constipa-
tion in 10%.
4. Solifenacin (Vesicare, 5 to 10 mg daily) and
darifenacin (Enablex, 7.5 to 15 mg daily) are
approved for overactive bladder. Solifenacin
and darifenacin are more selective for the M-3
muscarinic receptor in the bladder. Inconti-
nence episodes decrease with solifenacin,
similar to tolterodine (58%). The rate of dry
mouth is 14% and the rate of constipation is
7%.
5. Duloxetine (Cymbalta) is a serotonin and
norepinephrine reuptake inhibitor that is only
approved for major depression and
neuropathic pain. It stimulates pudendal motor
neuron alpha adrenergic and 5-
hydroxytryptamine-2 receptors. 40 mg twice
daily results in significant decreases in the
frequency of incontinence compared with pla-
cebo (50 to 54%). Nausea is common.
Duloxetine is contraindicated in chronic liver
disease.
B. Stress incontinence may be treated with topi-
cal estrogen. Up to 2 g of vaginal cream daily,
intravaginal estrogen rings, or dissolving tablets
(Vagifem) are effective for urinary incontinence.
Topical estrogen is applied as 0.3 mg of conju-
gated estrogens or 0.5 mg of estradiol daily for
three weeks, and then twice a week thereafter.

Medications Used to Treat Urinary Incontinence

Drug Dosage

Stress Incontinence

Estrogen dissolving tab- One tablet inserted vaginally

lets (Vagifem) once daily for the first two
weeks. Then one tablet twice
weekly

Vaginal estrogen ring Insert into vagina every three

(Estring) months

Vaginal estrogen cream 0.5 g, apply in vagina every

night

Overactive bladder

Oxybutynin transdermal 39 cm2 patch 2 times/week

(Oxytrol)

Oxybutynin ER (Ditropan 5 to 15 mg, every morning

XL)

Tolterodine LA (Detrol LA) 2-4 mg qd

Generic oxybutynin 2.5 to 10 mg, two to four

times daily

Tolterodine (Detrol) 1 to 2 mg, two times daily

Trospium (Sanctura) 20 mg twice daily

Solifenacin (Vesicare) 5 to 10 mg daily

Darifenacin (Enablex) 7.5 to 15 mg daily

Duloxetine (Cymbalta) 20 mg twice daily, and in-

creasing to 40 mg twice daily
after two weeks

VII. Surgery
A. Urge incontinence. Potential surgical treat-
ments for severe cases of intractable urge uri-
nary incontinence are sacral nerve modulation
and augmentation cystoplasty; however, these
are not first-line treatments.
B. Stress incontinence. Surgery offers the highest
cure rates for stress urinary incontinence. How-
ever, it is invasive and potentially morbid.
1. Bladder neck suspension procedures such
as the transvaginal Burch colposuspension
are used to treat urethral hypermobility and
stress urinary incontinence.
2. Sling procedures (using material to support
the urethra or bladder neck) including tension-
free vaginal tape (TVT) are increasingly being
used for stress incontinence in women.
3. Periurethral bulking injections with collagen
are preferable for intrinsic sphincter defi-
ciency.
VIII. Continence pessaries may benefit women with
stress urinary incontinence related to pelvic floor
prolapse or laxity. The use of these devices may
be very appealing to women, who wish to avoid
surgery.
References: See page 208.

Acute Cystitis
Cystitis is an infection of the bladder. Acute cystitis in the
healthy nonpregnant adult woman is considered to be
uncomplicated. A complicated infection is associated
with a condition that increases the risk of failing therapy.
About 7.8% of girls and 1.6% of boys have had a symp-
tomatic UTI. Approximately 50 to 60% of adult women
have had a UTI at some time during their life. Young
sexually active women have 0.5 episodes of acute cysti-
tis per year.

I. Microbiology Clinical features

A. Escherichia coli is the causative pathogen in 80
to 85% of episodes of acute uncomplicated cysti-
tis. Staphylococcus saprophyticus is responsible
for most other episodes, while Proteus mirabilis,
Klebsiella species, enterococci or other
uropathogens are isolated from a small propor-
tion of patients.
B. Acute uncomplicated cystitis is characterized by
dysuria, usually in combination with frequency,
urgency, suprapubic pain, and/or hematuria.
Fever (>38ºC), flank pain, costovertebral angle
tenderness, and nausea or vomiting suggest
pyelonephritis
C. Vaginitis should be considered if there is vaginal
discharge or odor, pruritus, dyspareunia, external
dysuria, and the absence of frequency or ur-
gency.
II. Diagnosis
A. Physical examination should include tempera-
ture, abdominal examination, and assessment for
costovertebral angle tenderness. A pelvic exami-
nation is indicated if symptoms of urethritis or
vaginitis are present.
B. Urinalysis. Pyuria is usually present with acute
cystitis; its absence strongly suggests a noninfec-
tious cause for the symptoms. An unspun voided
 midstream urine specimen should be examined
with a hemocytometer; 10 or more leukocytes per
mm3 is considered abnormal. White blood cell
casts in the urine are diagnostic of upper tract
infection. Hematuria is common with UTI but not
in urethritis or vaginitis. Microscopic evaluation of
the urine for bacteriuria is generally not recom-
mended for acute uncomplicated cystitis because
pathogens in low quantities <104 CFU/mL) are
difficult to find on the wet mount or Gram stain.
C. Indications for voided midstream urine cul-
tures
1. Suspected complicated infection.
2. The symptoms are not characteristic of UTI.
3. The patient has persistent symptoms of UTI
following treatment.
4. UTI symptoms recur less than one month after
treatment of a previous UTI.
D. Acute urethral syndrome. A CFU count
>102/mL should be considered positive on a mid-
stream urine specimen in women with acute
symptoms and pyuria. Some women with acute
dysuria have neither bacteriuria nor pyuria. The
symptoms usually resolve after antimicrobial
therapy.
E. Urine dipsticks
1. Dipsticks detect the presence of leukocyte
esterase and nitrite; the former detect pyuria
and the latter Enterobacteriaceae which con-
vert urinary nitrate to nitrite. The leukocyte
esterase test is a practical screening test with
a sensitivity of 75 to 96% and specificity of 94
to 98%. A microscopic evaluation for pyuria or
a culture is indicated with a negative leukocyte
esterase test with urinary symptoms.
2. The nitrite test is fairly sensitive and specific
for detecting >105 Enterobacteriaceae CFU
per mL of urine. However, it lacks adequate
sensitivity for detection of "low count" UTIs, or,
in some cases, infections caused by common
uropathogenic species.
III. Treatment
A. E. coli Resistance
1. One-third or more of isolates demonstrate
resistance to ampicillin and sulfonamides;
these agents should not be used for empiric
therapy. An increasing proportion of
uropathogens demonstrate resistance to
trimethoprim and/or TMP-SMX.
2. The prevalence of resistance to nitrofurantoin
among E. coli is less than 5%, although non-E.
coli uropathogens are often resistant.
3. Resistance to the fluoroquinolones remains
well below 5%.
B. S. saprophyticus resistance. Three% are resis-
tant to TMP-SMX, 1% to cephalothin, 0% to nitro-
furantoin, and 0.4% to ciprofloxacin.
C. Recommendation
1. Because of increasing fluoroquinolone resis-
tance, TMP-SMX should be the first-line treat-
ment for acute cystitis if the woman:
a. Has no history of allergy to the drug.
b. Has not been on antibiotics, especially
TMP-SMX, in the past three months.
c. Has not been hospitalized recently.
d. If the prevalence of E. coli resistance to
TMP-SMX in the area is not known to be
more than 20% among women with acute
uncomplicated cystitis.
2. A fluoroquinolone is an appropriate choice
for women who have an allergy to TMP-SMX
or risk factors for TMP-SMX resistance and
who have moderate to severe symptoms.

Oral Antibiotics for Acute Uncomplicated Cystitis

Drug, dose Dose and Duration

interval

Levofloxacin 250 mg q24h 3 days

(Levaquin)

Ciprofloxacin 100 to 250 mg 3 days

(Cipro) q12h OR 3 days
500 mg q24h

Gatifloxacin 400 mg single 3 days

(Tequin) dose OR
200 mg q24h

Trimethoprim- 160/800 mg 3 days

sulfamethoxaz q12h
ole (Bactrim)

Trimethoprim 100 mg q12h 3 days

Cefpodoxime 100 mg q12h 3-7days

proxetil
(Vantin)

Nitrofurantoin 50 mg q6h 7 days

macrocrystals
(Macrobid)

Nitrofurantoin 100 mg q12h 7 days

monohydrate
macrocrystals
(Macrobid)

Amoxicillin- 500 mg q12h 7 days

clavulanate
(Augmentin)

3. Nitrofurantoin (Macrodantin [for seven

days]) should be used for women with mild-to-
moderate symptoms who have allergy to TMP-
SMX or risk factors for TMP-SMX resistance.
4. Urinary analgesia (phenazopyridine [Pyrimi-
dine] 200 mg orally TID) is offered to those
with severe dysuria (10%). Phenazopyridine is
usually given for only one to two days.
5. Routine post-treatment cultures in non-preg-
nant women who have become asymptomatic
after an episode of cystitis are not indicated. In
patients whose symptoms do not resolve,
urine culture and antimicrobial susceptibility
testing should be performed. Empiric therapy
should include a fluoroquinolone unless such
an agent was used initially.
IV. Acute complicated cystitis
A. Urinary tract infection may lead to serious compli-
cations in the person who is pregnant, very
young or old, diabetic, immunocompromised, or
who has an abnormal genitourinary tract.
B. Clinical presentation. Acute complicated cystitis
generally presents with dysuria, frequency, ur-
gency, suprapubic pain, and/or hematuria. Fever
(>38ºC), flank pain, costovertebral angle tender-
ness, and nausea or vomiting suggest the infec-
tion has extended beyond the bladder.
C. Bacteriology. The spectrum of uropathogens
causing complicated cystitis is much broader
than that causing uncomplicated cystitis. Infec-
tion with Proteus, Klebsiella, Pseudomonas,
Serratia, and Providencia species, and
enterococci, staphylococci and fungi is more
common in complicated cystitis. These
uropathogens, including E. coli, are much more
likely to be resistant to common antimicrobials.
D. Diagnosis. Pyuria is present in almost all pa-
tients with complicated cystitis. Urine cultures
with susceptibility testing should be obtained in
complicated cystitis. A Gram stain may be helpful
since the presence of Gram positive cocci, sug-
gestive of enterococci, may influence the choice
of empiric antibiotics.
E. Treatment
1. Complicated cystitis should be treated with an
oral fluoroquinolone such as ciprofloxacin,
levofloxacin, or gatifloxacin. The
fluoroquinolones are well tolerated, provide a
broad spectrum of activity covering most ex-
pected pathogens (including P. aeruginosa),
and achieve high levels in the urine and uri-
nary tract tissue. The recommended dose for
ciprofloxacin (Cipro) is 500 mg PO twice daily,
for levofloxacin (Levaquin) is 500 mg PO once
daily, and for gatifloxacin (Tequin) is 400 mg
PO once daily, each for 7 to 14 days.
2. Amoxicillin, nitrofurantoin and sulfa drugs are
poor choices for empiric therapy in compli-
cated cystitis because of the high prevalence
of resistance.
3. Parenteral therapy is occasionally indicated for
the treatment of complicated cystitis caused by
multiply-resistant uropathogens, or for those
patients who are allergic or intolerant to
fluoroquinolones. Parenteral levofloxacin (500
mg) or gatifloxacin (400 mg), ceftriaxone (1 g),
or an aminoglycoside (3 to 5 mg/kg of
gentamicin or tobramycin) can be adminis-
tered once daily. Patients initially given
parenteral therapy can be switched to oral
agents, usually a fluoroquinolone, after clinical
improvement.
4. Gram positive cocci, suggestive of
enterococci, may require the addition of
ampicillin (1 g every six hours) or amoxicillin
(500 mg PO every eight hours) to a treatment
regimen.
5. If the patient does not show improvement
within 24 to 48 hours, a repeat urine culture
and ultrasound or computerized tomography
should be considered to rule out urinary tract
pathology.
6. The recommended duration of treatment for
acute complicated cystitis is 7 to 14 days. A
follow-up urine culture is not indicated in the
asymptomatic patient.
V. Cystitis in young men. A small number of 15- to 50-
year-old men suffer acute uncomplicated UTIs. Risk
factors include homosexuality, intercourse with an
infected female partner, and lack of circumcision.
A. Dysuria, frequency, urgency, suprapubic pain, or
hematuria are typical of cystitis in men. The ab-
sence of pyuria suggests a non-infectious diag-
nosis. A midstream urine culture is recom-
mended.
B. Other causes of infection. Urethritis must be
considered in sexually active men; examination
for penile ulcerations and urethral discharge,
evaluation of a urethral swab specimen Gram
stain, and diagnostic tests for N. gonorrheae and
C. trachomatis are warranted. A urethral Gram
stain demonstrating leukocytes and predominant
Gram negative rods suggests E. coli urethritis.
C. Chronic prostatitis should also be considered,
particularly in men who have had recurrent UTIs.
D. Treatment of cystitis. The etiologic agents
causing uncomplicated urinary tract infections in
men are similar to those in women. Thus, the
TMP-SMX (Bactrim) is appropriate for empiric
use in men, although 7-day regimens are recom-
mended. Nitrofurantoin and beta-lactams should
not be used in men with cystitis since they do not
achieve reliable tissue concentrations and would
be ineffective for occult prostatitis.
Fluoroquinolones provide the best antimicrobial
spectrum and prostatic penetration.
References: See page 208.

Acute Pyelonephritis
Urinary tract infections (UTIs) are common, especially in
young children and sexually active women. UTI is de-
fined either as a lower tract (acute cystitis) or upper tract
(acute pyelonephritis) infection.

I. Clinical features
A. Acute uncomplicated pyelonephritis is suggested
by flank pain, nausea/vomiting, fever (>38ºC)
and/or costovertebral angle tenderness. Fre-
quency, dysuria, and suprapubic pain are found in
the majority of patients whether infection is local-
ized to the upper or lower tract.
B. Fever >37.8ºC is strongly correlated with acute
pyelonephritis. The examination should focus on
temperature, abdomen, and costovertebral angle
tenderness.
C. Pelvic examination may be indicated since pelvic
inflammatory disease is a condition often mistaken
for acute uncomplicated pyelonephritis. Pelvic
examination does not need to be performed, how-
ever, in a woman with unilateral CVA pain and
tenderness, fever, pyuria, and no vaginal symp-
toms.
 Risk Factors for Occult Renal Infection or a Com-
plicated Urinary Tract Infection

Male sex Functional or anatomic

Elderly abnormality of the uri-
Presentation in emer- nary tract
gency department Recent antimicrobial
Hospital-acquired infec- use
tion Symptoms for more
Pregnancy than seven days at pre-
Indwelling urinary cathe- sentation
ter Diabetes mellitus
Recent urinary tract in- Immunosuppression
strumentation
Childhood urinary tract
infection

II. Laboratory features

A. Pyuria is present in virtually all women with acute
pyelonephritis; its absence strongly suggests an
alternative diagnosis. Hematuria is common with
urinary tract infection but not in urethritis or vagini-
tis. Most patients with acute pyelonephritis have
leukocytosis and an elevated erythrocyte sedi-
mentation rate and serum C-reactive protein.
B. Some patients with pyelonephritis may have col-
ony counts of 103 to 104 CFU per mL. Blood cul-
tures are positive in 10 to 20% of women with
acute uncomplicated pyelonephritis.
C. A urinalysis should be performed to look for
pyuria. White cell casts indicate a renal origin for
the pyuria. Gram stain, usually performed on spun
urine, may distinguish Gram negative from Gram
positive infections. A pregnancy test should be
performed if there is missed menses or lack of
contraception.
D. Urine culture and antimicrobial susceptibility test-
ing should be performed routinely in acute
pyelonephritis.
E. Rapid methods for detection of bacteriuria, such
as the nitrite test, should not be relied upon in the
evaluation of patients with suspected
pyelonephritis because tests lack adequate sensi-
tivity for detection of “low count” urinary tract infec-
tion and common uropathogenic species. The
nitrite test has a sensitivity of 35 to 80% and does
not detect organisms unable to reduce nitrate to
nitrite, such as enterococci and staphylococci.
F. Blood cultures are limited to those patients who
warrant hospitalization.
III. Treatment. Microbiology of acute uncomplicated
upper and lower urinary tract infection is rather
limited with Escherichia coli accounting for 70 to
95% of infections and Staphylococcus
saprophyticus 5 to 20%.
A. Indications for admission to the hospital in-
clude:
1. Inability to maintain oral hydration or take medi-
cations.
2. Patient noncompliance.
3. Uncertainty about the diagnosis.
4. Severe illness with high fevers, pain, and marked
debility.
5. Outpatient therapy should generally be reserved
for nonpregnant women with mild-to-moderate
uncomplicated pyelonephritis who are compliant.
B. Empiric antibiotic therapy
1. Ampicillin and sulfonamides should not be used
for empiric therapy because of the high rate of
resistance. An increasing proportion of
uropathogens demonstrate resistance to
trimethoprim-sulfamethoxazole. In comparison,
resistance to the fluoroquinolones and
aminoglycosides is very low in uncomplicated
UTIs.
2. Oral agents. In patients with acute uncompli-
cated pyelonephritis, an oral fluoroquinolone,
such as ciprofloxacin (500 mg PO BID),
levofloxacin (Levaquin [250 to 500 mg PO QD]),
or gatifloxacin (Tequin [400 mg PO QD]), is rec-
ommended for outpatients as initial empiric treat-
ment of infection caused by Gram negative ba-
cilli. The newer fluoroquinolones, sparfloxacin,
trovafloxacin and moxifloxacin, should be
avoided because they may not achieve adequate
concentrations in urine.
a. Trimethoprim, trimethoprim-sulfamethoxazole
or other agents can be used if the infecting
strain is known to be susceptible. If
enterococcus is suspected by the presence of
small Gram positive cocci on Gram stain,
amoxicillin (500 mg PO TID) should be added
to the treatment regimen until the causative
organism is identified.
b. Cefixime (Suprax) and cefpodoxime proxetil
(Vantin) also appear to be effective for the
treatment of acute uncomplicated
pyelonephritis. Cefixime is less effective
against S. saprophyticus. Nitrofurantoin
should not be used for the treatment of
pyelonephritis since it does not achieve reli-
able tissue levels.

Parenteral Regimens for Empiric Treatment of

Acute Uncomplicated Pyelonephritis

Antibiotic, dose Interval

Ceftriaxone (Rocephin), 1 g q24h

Ciprofloxacin (Cipro), 200-400 q12h

mg

Levofloxacin (Levaquin), 250- q24h

500 mg

Ofloxacin (Floxin), 200-400 mg q12 h

Gatifloxacin (Tequin), 400 mg q24h

Gentamicin, 3-5 mg/kg q24h

(+ampicillin)

Gentamicin, 1 mg per kg q8h

(+ampicillin)

Ampicillin, 1-2 g (plus q6h

gentamicin)*

Aztreonam (Azactam), 1 g q8-12h

*
Recommended regimen if enterococcus suspected.

3. Parenteral therapy. For hospitalized patients,

ceftriaxone (Rocephin [1 gram IV QD]) is recom-
mended if enterococcus is not suspected.
Aminoglycosides (3 to 5 mg/kg) given once daily
provide a therapeutic advantage compared with
beta lactams because of their marked and sus-
tained concentration in renal tissue.
a. Ciprofloxacin, ofloxacin, levofloxacin and
gatifloxacin are also effective for the
parenteral treatment of uncomplicated
pyelonephritis but should be used orally if the
patient is able to tolerate oral medications
since the costs are lower and serum levels
are equivalent.
b. If enterococcus is suspected based upon the
Gram stain, ampicillin (1 to 2 g IV Q6h) plus
gentamicin (1.0 mg/kg IV Q8h) or piperacillin-
tazobactam (3.375 g IV Q8h) are reasonable
broad spectrum empiric choices. Once-daily
dosing of aminoglycosides is not recom-
mended for serious probable enterococcal
infection since this regimen may not provide
adequate synergy against the organism.
C. Duration. Patients with acute uncomplicated
pyelonephritis can often be switched to oral therapy
at 24 to 48 hours. Patients should be evaluated for
complicated pyelonephritis if they fail to defervesce
or if bacteremia persists. A 14-day regimen is rec-
ommended. In sicker patients, a longer duration of
treatment may be required (14 to 21 days).
D. Posttreatment follow-up cultures in an asymp-
tomatic patient are not indicated. In women whose
pyelonephritis symptoms resolve but recur within
two weeks, a repeat urine culture and antimicrobial
susceptibility testing should be performed. If the
initially infecting species is isolated again with the
same susceptibility profile, a renal ultrasound or
computed tomographic (CT) scan should be per-
formed. Retreatment with a two-week regimen us-
ing another agent should be considered.
E. Urologic evaluation
1. Routine urologic investigation of young healthy
women with acute uncomplicated pyelonephritis
is generally not recommended. Ultrasound or CT
scan should be considered if the patient remains
febrile or has not shown clinical improvement
after 72 hours of treatment. CT scan or renal
ultrasound should be performed after two recur-
rences of pyelonephritis.
IV. Acute complicated pyelonephritis
A. Clinical features. In addition to flank pain, dysuria
and fever, complicated urinary tract infections may
also be associated with malaise, fatigue, nausea, or
abdominal pain.
B. A urine Gram stain and culture should always be
performed in patients with suspected complicated
UTI. A colony count threshold of >103 CFU per mL
should be used to diagnose symptomatic compli-
cated infection except when urine cultures are ob-
tained through a newly-inserted catheter in which
case a level of >10(2) CFU per mL is evidence of
infection.
C. Microbiology. E. coli is still the predominant
uropathogen, but other uropathogens, including
Citrobacter sp, Enterobacter sp, Pseudomonas
aeruginosa, enterococci, Staphylococcus aureus,
and fungi account for a higher proportion of cases
compared with uncomplicated urinary tract infec-
tions.
D. Treatment. Patients with complicated
pyelonephritis, including pregnant women, should
be managed as inpatients. Underlying anatomic
(eg, stones, obstruction), functional (eg, neurogenic
bladder), or metabolic (eg, poorly controlled diabe-
tes) defects must be corrected.
1. In contrast to uncomplicated UTI, S. aureus is
relatively more likely to be found. For those pa-
tients with mild to moderate illness who can be
treated with oral medication, a fluoroquinolone is
the best choice for empiric therapy.
Fluoroquinolones are comparable or superior to
other broad spectrum regimens, including
parenteral therapy. Sparfloxacin, trovafloxacin
and moxifloxacin are not effective.
2. Antimicrobial regimen can be modified when the
infecting strain susceptibilities are known. Pa-
tients on parenteral regimens can be switched to
oral treatment, generally a fluoroquinolone, after
clinical improvement. Patients undergoing effec-
tive treatment with an antimicrobial to which the
infecting pathogen is susceptible should have
definite improvement within 24 to 48 hours and,
if not, a repeat urine culture and imaging studies
should be performed.
3. At least 10 to 14 days of therapy is recom-
mended. Urine culture should be repeated one
to two weeks after the completion of therapy.
Suppressive antibiotics may be considered with
complicated pyelonephritis and a positive follow-
up urine culture.

Parenteral Regimens for Empiric Treatment of

Acute Complicated Pyelonephritis

Antibiotic, dose Interval

Cefepime (Maxipime) , 1 g q12 hours

Ciprofloxacin (Cipro), 400 q12 hours
mg q24 hours
Levofloxacin (Levaquin), q12 hours
500 mg q24 hours
Ofloxacin (Floxin), 400 mg q24 hours
Gatifloxacin (Tequin), 400 q8 hours
mg q6 hours
Gentamicin, 3-5 mg/kg (+ q8 hours
ampicillin)* q6-8 hours
Gentamicin, 1 mg per kg (+ q6-8 hours
ampicillin)*
Ampicillin, 1-2 g (+
gentamicin)*
Ticarcillin-clavulante
(Timentin), 3.2 g
Piperacilin-tazobactam
(Zosyn), 3.375 g*
Imipenem-cilastatin, 250-
500 mg

*Recommended regimen if enterococcus suspected

References: See page 208.

Pubic Infections
I. Molluscum contagiosum
A. This disease is produced by a virus of the pox
virus family and is spread by sexual or close per-
sonal contact. Lesions are usually asymptomatic
and multiple, with a central umbilication. Lesions
can be spread by autoinoculation and last from 6
months to many years.
B. Diagnosis. The characteristic appearance is ade-
quate for diagnosis, but biopsy may be used to
confirm the diagnosis.
 C. Treatment. Lesions are removed by sharp dermal
curette, liquid nitrogen cryosurgery, or
electrodesiccation.
II. Pediculosis pubis (crabs)
A. Phthirus pubis is a blood sucking louse that is
unable to survive more than 24 hours off the body.
It is often transmitted sexually and is principally
found on the pubic hairs. Diagnosis is confirmed
by locating nits or adult lice on the hair shafts.
B. Treatment
1. Permethrin cream (Elimite), 5% is the most
effective treatment; it is applied for 10 minutes
and washed off.
2. Kwell shampoo, lathered for at least 4 min-
utes, can also be used, but it is contraindicated
in pregnancy or lactation.
3. All contaminated clothing and linen should be
laundered.
III. Pubic scabies
A. This highly contagious infestation is caused by the
Sarcoptes scabiei (0.2-0.4 mm in length). The
infestation is transmitted by intimate contact or by
contact with infested clothing. The female mite
burrows into the skin, and after 1 month, severe
pruritus develops. A multiform eruption may de-
velop, characterized by papules, vesicles, pus-
tules, urticarial wheals, and secondary infections
on the hands, wrists, elbows, belt line, buttocks,
genitalia, and outer feet.
B. Diagnosis is confirmed by visualization of burrows
and observation of parasites, eggs, larvae, or red
fecal compactions under microscopy.
C. Treatment. Permethrin 5% cream (Elimite) is mas-
saged in from the neck down and remove by
washing after 8 hours.
References: See page 208.

Pelvic Inflammatory Disease

Pelvic inflammatory disease (PID) is an acute infection
of the upper genital tract structures in women, involving
the uterus, oviducts, and ovaries. PID usually is a
community-acquired infection initiated by a sexually
transmitted agent. The estimated number of cases of
PID in women 15 to 44 years of age in the United States
was 168,837 in 2003.

I. Clinical features
A. Lower abdominal pain is the cardinal presenting
symptom in women with PID. The recent onset of
pain that worsens during coitus or with jarring
movement may be the only presenting symptom of
PID; the onset of pain during or shortly after men-
ses is particularly suggestive. The abdominal pain
is usually bilateral and rarely of more than two
weeks' duration.
B. Abnormal uterine bleeding occurs in one-third or
more of patients with PID. New vaginal discharge,
urethritis, proctitis, fever, and chills can be associ-
ated signs. The presence of PID is less likely if
symptoms referable to the bowel or urinary tract
predominate.
C. Risk factors for sexually transmitted diseases:
1. Age less than 25 years
2. Young age at first sex
3. Nonbarrier contraception
4. New, multiple, or symptomatic sexual partners
5. Oral contraception
6. Cervical ectopy
D. Factors that facilitate pelvic inflammatory dis-
ease:
1. Previous episode of PID
2. Sex during menses
3. Vaginal douching
4. Bacterial vaginosis
5. Intrauterine device
E. Physical examination. Only one-half of patients
with PID have fever. Abdominal examination re-
veals diffuse tenderness greatest in the lower
quadrants, which may or may not be symmetrical.
Rebound tenderness and decreased bowel sounds
are common. Marked tenderness in the right upper
quadrant does not exclude PID, since 10% of
these patients have perihepatitis (Fitz-Hugh Curtis
syndrome).
F. Pelvic examination. Purulent endocervical dis-
charge and/or acute cervical motion and adnexal
tenderness with bimanual examination is strongly
suggestive of PID. Significant lateralization of
adnexal tenderness is uncommon in PID.
G. Subclinical pelvic inflammatory disease. Lower
genital tract infection with gonorrhea, chlamydia, or
bacterial vaginosis is a risk factor for subclinical
PID, defined by the presence of neutrophils and
plasma cells in endometrial tissue.
II. Diagnostic considerations
A. Laparoscopy is recommended for the following:
1. A sick patient with high suspicion of a competing
diagnosis (appendicitis)
2. An acutely ill patient who has failed outpatient
treatment for PID
3. Any patient not clearly improving after 72 hours
of inpatient treatment for PID. Consent for
laparotomy at the same procedure should be
obtained in advance for these patients.
B. Diagnostic criteria. The index of suspicion for the
clinical diagnosis of PID should be high, especially
in adolescent women, even if they deny sexual
activity. Empiric treatment is recommended for
women with abdominal pain who have at least one
of the following:
1. Cervical motion tenderness or uterine/adnexal
tenderness
2. Oral temperature >101 F (>38.3 C)
3. Peripheral leukocytosis/left shift
4. Abnormal cervical or vaginal mucopurulent dis-
charge
5. Presence of white blood cells (WBCs) on saline
microscopy of vaginal secretions
6. Elevated erythrocyte sedimentation rate
7. Elevated C-reactive protein
III. Differential diagnosis. In addition to PID, the
differential diagnosis of lower abdominal pain in a
young woman includes the following conditions:
A. Gastrointestinal: Appendicitis, cholecystitis, consti-
pation, gastroenteritis, inflammatory bowel disease
B. Renal: Cystitis, pyelonephritis, nephrolithiasis,
urethritis
C. Obstetric/Gynecologic: Dysmenorrhea, ectopic
pregnancy, intrauterine pregnancy complication,
ovarian cyst, ovarian torsion, ovarian tumor.

Differential Diagnosis of Pelvic Inflammatory

Disease

Appendicitis Irritable bowel syndrome

Ectopic pregnancy Somatization
Hemorrhagic ovarian cyst Gastroenteritis
Ovarian torsion Cholecystitis
Endometriosis Nephrolithiasis
Urinary tract Infection

IV. Diagnostic testing

A. Laboratory testing for patients suspected of PID
always begins with a pregnancy test to rule out
ectopic pregnancy and complications of an
intrauterine pregnancy. A urinalysis (preferably on
a catheterized specimen) and a stool for occult
blood should be obtained since abnormalities in
either lessen the probability of PID. Although PID
is usually an acute process, fewer than one-half
of PID patients exhibit leukocytosis. A hematocrit
of less than 0.30 makes PID less likely.
B. Gram stain and microscopic examination of
vaginal discharge. If a cervical Gram stain is posi-
tive for Gram negative intracellular diplococci, the
probability of PID greatly increases; if negative, it
is of little use.
C. Increased white blood cells (WBC) in vaginal fluid
is the most sensitive single laboratory test for PID
(78% for >3 WBC per high power field. However,
the specificity is only 39%.
D. Recommended laboratory tests:
1. Pregnancy test
2. Microscopic exam of vaginal discharge in sa-
line
3. Complete blood counts
4. Nucleic acid amplification tests for chlamydia
and gonococcus
5. Urinalysis
6. Fecal occult blood test
7. C-reactive protein (optional)
8. Ultrasounds are reserved for acutely ill patients
with PID in whom a pelvic abscess is a consid-
eration.
V. Treatment and sequelae of pelvic inflammatory
disease
A. Outpatient therapy. The CDC recommends ei-
ther oral ofloxacin (Floxin, 400 mg twice daily) or
levofloxacin (Levaquin, 500 mg once daily) with or
without metronidazole (Flagyl) 500 mg twice daily)
for 14 days. Metronidazole is added when anaer-
obic coverage is of concern. Beyond 48 hours of
symptoms, the most frequent isolates are
anaerobes.
B. An alternative is an initial single dose of
ceftriaxone (Rocephin, 250 mg IM), cefoxitin
(Mefoxin, 2 g IM plus probenecid 1 g orally), or
another parenteral third-generation
cephalosporin, followed by doxycycline (100 mg
orally twice daily) with or without metronidazole
for 14 days. The combination of amoxicillin-
clavulanate and doxycycline is also an alternative
that has achieved short-term clinical response.
For patients younger than 18 years of age, one of
the alternative regimens should be used since
neither ofloxacin nor levofloxacin is approved for
systemic use in this age group.
C. For women younger than 18 years treatment
consists of an initial single dose of ceftriaxone
(Rocephin, 250 mg IM) or cefoxitin (Mefoxin, 2 g
IM plus probenecid 1 g orally), or another
parenteral third-generation cephalosporin, fol-
lowed by doxycycline (100 mg orally twice daily)
with or without metronidazole for 14 days. For
those who are unlikely to complete at least seven
days of doxycycline, some providers suggest
administration of azithromycin 1 g PO should be
given at the time of parenteral adminstration of
cephalosporin to ensure eradication of chlamydia.

D. For women >18 years azithromycin

(Zithromax) 1 g PO should be given for
Chlamydia coverage, and either cefixime
(Suprax) 400 mg PO or ceftriaxone (Rocephin)
125 mg IM (for gonococcus coverage) given for
one dose by directly observed therapy, followed
by amoxicillin-clavulanate 875 mg PO twice daily
for 7 to 10 days. For penicillin-allergic patients, a
fluoroquinolone or spectinomycin may be used for
initial single-dose gonococcus coverage, followed
by doxycycline and metronidazole for 14 days.
E. Reevaluation two to three days after the initiation
of therapy to assure accuracy of diagnosis and
response to therapy is an extremely important
aspect of outpatient treatment of PID.
F. Inpatient therapy. The CDC suggest either of the
following regimens:
1. Cefotetan (Cefotan, 2 g IV every12h) or
cefoxitin (Mefoxin, 2 g IV every 6h) plus
doxycycline (100 mg IV or PO every 12h), or
2. Clindamycin (900 mg IV every 8h) plus
gentamicin loading dose (2 mg/kg of body
weight) followed by a maintenance dose (1.5
mg/kg) every 8 hours. Single daily dosing of
gentamicin may be substituted.
3. Alternative regimens:
a. Ofloxacin (Floxin, 400 mg IV every12h) or
levofloxacin (Levoquin, 500 mg IV daily)
with or without metronidazole (Flagyl, 500
mg IV every 8h), or
b. Ampicillin-sulbactam (Unasyn, 3 g IV every
6h) plus doxycycline (100 mg IV or PO
every12h).
c. Ofloxacin has been studied as
monotherapy for the treatment of PID; how-
ever, due to concerns regarding its lack of
activity against anaerobic flora, some clini-
cians prefer to also add metronidazole.
Ampicillin-sulbactam plus oral doxycycline
is effective coverage against Chlamydia
trachomatis, Neisseria gonorrhoeae, and
anaerobes.
4. Parenteral administration of antibiotics should
be continued for 24 hours after a clear clinical
response, followed by doxycycline (100 mg PO
BID) or clindamycin (450 mg PO QID) for a
total of 14 days.
G. Recommended regimens:
1. Levofloxacin (Levoquin, 500 mg IV Q24h)
plus metronidazole (500 mg IV Q8h)
2. A broad spectrum cephalosporin plus
doxycycline with or without metronidazole
3. Ertapenem (Invanz, 1 g IV Q24h)
H. For patients younger than 18 years of age, the
second regimen should be used since
levofloxacin is not approved for use in this age
group when other effective alternatives are avail-
able.
I. Some providers prescribe azithromycin
(Zithromax, 1 g PO once) as soon as the patient
is tolerating oral intake if the patient is unlikely to
comply with doxycycline administration.
Parenteral therapy should continue until the pel-
vic tenderness is absent (two to five days).
J. Treatment for PID must be accompanied by a
discussion of sexually transmitted infections, part-
ner treatment, and future safe sex practices. Male
 sex partners of women with PID should be exam-
ined and empirically treated if they had sexual
contact during the preceding 60 days. Other im-
portant components of the evaluation include:
1. Serology for human immunodeficiency virus
(HIV)
2. Papanicolaou smear
3. Hepatitis B surface antigen determination and
initiation of the vaccine series for patients who
are antigen negative and unvaccinated
4. Hepatitis C virus serology
5. Serologic tests for syphilis
References: See page 208.

Genital Chlamydia Trachomatis

Infections
Chlamydia trachomatis is the most common sexually
transmitted genital infection. Infants born to mothers
through an infected birth canal can develop conjunctivitis
and pneumonia. These syndromes are caused by the C.
trachomatis serovars B and D through K. The L serovars
cause lymphogranuloma venereum (LGV), a genital
ulcer syndrome. Chlamydia trachomatis serovars A to C
cause endemic trachoma, a common ocular infection in
the developing world.
I. Microbiology and epidemiology
A. C. trachomatis is a small gram-negative bacterium
and an obligate intracellular parasite.
B. Chlamydia cannot be cultured on artificial media;
tissue culture has been required. Rapid screening
tests are now available.
C. 4,000,000 cases of C. trachomatis infection occur
annually. C. trachomatis and Neisseria
gonorrhoeae cause similar clinical syndromes, but
chlamydia infections tend to have fewer acute
symptoms and more significant long-term compli-
cations.
D. Prevalence. The rates of chlamydia are highest in
adolescent women. Between 18 and 26 years of
age, the prevalence of chlamydial infection is
4.2%. The highest rates are in African American
women (14%) and are higher in women than men.
E. Risk factors for Chlamydia trachomatis infec-
tion:
1. Adolescents and young adults
2. Multiple sex partners or a partner with other
partners during the last three months or a re-
cent new sex partner
3. Inconsistent use of barrier contraceptives
4. Clinical evidence of mucopurulent cervicitis
5. Cervical ectopy
6. Unmarried status
7. History of prior sexually transmitted disease
8. Lower socioeconomic class or education not
beyond high school.
II. Clinical manifestations
A. The majority of women with C. trachomatis infec-
tion are asymptomatic; however, cervicitis or pel-
vic inflammatory disease may occur.
B. Cervicitis. Cervical infection is the most common
chlamydial syndrome in women. More than 50%
of these women are asymptomatic. Vaginal dis-
charge, poorly differentiated abdominal pain, or
lower abdominal pain are the most frequent symp-
toms.
C. Physical examination is often unremarkable,
mucopurulent cervical discharge, cervical friability,
cervical edema, and endocervical ulcers may be
seen.
D. Perihepatitis (Fitzhugh-Curtis syndrome). Pa-
tients with chlamydia infection occasionally de-
velop perihepatitis, an inflammation of the liver
capsule and adjacent peritoneal surfaces.
Perihepatitis is more commonly seen in PID, oc-
curring in 5% of cases.
E. Pelvic inflammatory disease. 30% of women
with chlamydia infection will develop PID if left
untreated. While PID caused by N. gonorrhoeae
infection may be more acutely symptomatic, PID
due to C. trachomatis tends to cause higher rates
of infertility.
F. Pregnancy. Untreated chlamydia infection can
increase the risk for premature rupture of the
membranes and low birth weight. If the mother is
untreated, 20 to 50% of newborns will develop
conjunctivitis, and 10 to 20% will develop pneu-
monia.
III. Diagnosis
A. Nucleic acid amplification (NAAT) uses poly-
merase chain reaction (PCR). These sensitive
and specific tests have replaced poorly standard-
ized cell culture methods as the “gold standard.”
1. Another advantage of NAATs is the ability to
perform testing on urine as well as urethral
specimens. Since urine collection is
noninvasive, it is a preferred method.
2. The PCR assay has a sensitivity and specificity
of 83 and 99.5% for urine samples and 86 and
99.6% for cervical samples.
B. Antigen detection requires a swab from the cer-
vix or urethra. The sensitivity of this method is 80
to 95% compared to culture.
IV. Chlamydia screening
A. Clinical practice guidelines strongly recommend
routine chlamydia screening for sexually-active
women below the age of 25.
V. Treatment. Chlamydiae are susceptible to the
tetracyclines and the macrolides. Treatment efficacy
with recommended regimens is >95%.
A. Azithromycin (Zithromax, 1 g PO as a single dose)
or doxycycline (100 mg PO BID for 7 days) are the
two recommended regimens.
B. Alternative regimens include seven days of
erythromycin base (500 mg PO QID),
erythromycin ethylsuccinate (800 mg PO),
ofloxacin (300 mg PO BID), or levofloxacin (500
mg PO QD). Erythromycin is associated with sig-
nificant gastrointestinal side effects; ofloxacin and
levofloxacin are expensive alternatives.

Treatment of chlamydia trachomatis infection

and related syndromes

Urethritis, cervicitis, conjunctivitis, or proctitis

Azithromycin (Zithromax) 1 g oral once OR

Doxycycline 100 mg oral twice daily for seven days
Alternatives
Ofloxacin (Floxin) 300 mg oral twice daily for seven
days
Levofloxacin (Levaquin) 500 mg oral daily for seven
days
Erythromycin 500 mg oral four times daily for seven
days

Infection in pregnancy

Azithromycin (Zithromax) 1 g oral once OR

Amoxicillin 500 mg oral three times daily for seven
days
Alternatives
Erythromycin 500 mg oral four times daily for seven
days

Neonatal ophthalmia or pneumonia

Azithromycin 20 mg/kg oral once daily for three days

Alternatives
Erythromycin 12.5 mg/kg oral four times daily for 14
days§

Lymphogranuloma venereum

Doxycycline 100 mg oral twice daily for 21 days

Alternatives
Erythromycin 500 mg oral four times daily for 21 days

C. Adjunctive measures:
1. Presumptive treatment of partners
2. Evaluation for other STDs (syphilis serology,
gonococcal testing)
3. HIV counseling and testing
4. Safer-sex counseling and condom provision
5. Contraception provision or referral
6. Test of cure. Testing for C. trachomatis following
treatment with azithromycin or doxycycline is not
recommended. Exceptions include:
a. Patients with persisting symptoms or
b. Those in whom compliance with the treat-
ment regimen is suspected.
c. Pregnant females
7. If a test for cure is performed, this should be
done more than three weeks after the comple-
tion of therapy.
8. Repeat screening should be considered within
the first three to four months after therapy is
completed or at least when the patient has her
next encounter with the healthcare system within
the first 12 months because patients who have
the disease once are at a higher risk for acquir-
ing it again.
References: See page 208.

Vaginitis
Approximately 8-18% of women report an episode of
vaginal symptoms each year. The etiology of vaginal
complaints includes infection of the vagina, cervix, and
upper genital tract, chemicals or irritants (eg, spermi-
cides or douching), hormone deficiency, and rarely sys-
temic diseases.

I. Clinical evaluation
A. Symptoms of vaginitis include vaginal discharge,
pruritus, irritation, soreness, odor, dyspareunia and
dysuria. Dyspareunia is a common feature of atro-
phic vaginitis. Abdominal pain is suggestive of
pelvic inflammatory disease and suprapubic pain is
suggestive of cystitis.
B. A new sexual partner increases the risk of acquir-
ing sexually transmitted diseases, such as
trichomonas, chlamydia, or Neisseria gonorrheae.
Trichomoniasis often occurs during or immediately
after the menstrual period; candida vulvovaginitis
often occurs during the premenstrual period.
C. Antibiotics and high-estrogen oral contraceptive
pills may predispose to candida vulvovaginitis;
increased physiologic discharge can occur with oral
contraceptives; pruritus unresponsive to antifungal
agents suggests vulvar dermatitis.
II. Physical examination
A. The vulva usually appears normal in bacterial
vaginosis. Erythema, edema, or fissure formation
suggest candidiasis, trichomoniasis, or dermatitis.
B. Trichomonas is associated with a purulent dis-
charge; candidiasis is associated with a thick, ad-
herent, “cottage cheese-like” discharge; and bacte-
rial vaginosis is associated with a thin, homoge-
neous, “fishy smelling” discharge. The cervix in
women with cervicitis is usually erythematous and
friable, with a mucopurulent dischage.
C. Abdominal or cervical motion tenderness is sug-
gestive of PID.
III. Diagnostic studies
A. Vaginal pH. The pH of the normal vaginal secre-
tions is 4.0 to 4.5. A pH above 4.5 suggests bacte-
rial vaginosis or trichomoniasis (pH 5 to 6), and
helps to exclude candida vulvovaginitis (pH 4 to
4.5).
B. Saline microscopy should look for candidal buds
or hyphae, motile trichomonads, epithelial cells
studded with adherent coccobacilli (clue cells), and
polymorphonuclear cells (PMNs). The addition of
10% potassium hydroxide to the wet mount is help-
ful in diagnosing candida vaginitis. Culture for
candida and trichomonas may be useful if micros-
copy is negative.
C. Cervical culture. A diagnosis of cervicitis, typically
due to Neisseria gonorrhoeae or Chlamydia
trachomatis, must always be considered in women
with purulent vaginal discharge. The presence of
high-risk behavior or any sexually transmitted dis-
ease requires screening for HIV, hepatitis B, and
other STDs.

Clinical Manifestations of Vaginitis

Candidal Vagi- Nonmalodorous, thick, white, "cottage

nitis cheese-like" discharge that adheres to vagi-
nal walls
Hyphal forms or budding yeast cells on wet-
mount
Pruritus
Normal pH (<4.5)

Bacterial Thin, dark or dull grey, homogeneous, mal-

Vaginosis odorous discharge that adheres to the vagi-
nal walls
Elevated pH level (>4.5)
Positive KOH (whiff test)
Clue cells on wet-mount microscopic evalua-
tion

Trichomonas Copious, yellow-gray or green, homogeneous

Vaginalis or frothy, malodorous discharge
Elevated pH level (>4.5)
Mobile, flagellated organisms and leukocytes
on wet-mount microscopic evaluation
Vulvovaginal irritation, dysuria
Atrophic Vagi- Vaginal dryness or burning
nitis

IV. Bacterial vaginosis

A. Incidence. Bacterial vaginosis is the most common
cause of vaginitis in women of childbearing age,
with prevalence of 5-60%.
B. Microbiology and risk factors. Bacterial vaginosis
represents a change in vaginal flora characterized
by a reduction of lactobacilli and an increase of
Gardnerella vaginalis, Mobiluncus species,
Mycoplasma hominis, anaerobic gram-negative
rods, and Peptostreptococcus species. Risk factors
for bacterial vaginosis include multiple or new sex-
ual partners, early age of first coitus, douching,
cigarette smoking, and use of an intrauterine con-
traceptive device.
C. Clinical features. Symptoms include a “fishy smell-
ing” discharge that is more noticeable after unpro-
tected intercourse. The discharge is off-white, thin,
and homogeneous. Pruritus and inflammation are
absent.
D. Complications
1. Pregnant women appear to be at higher risk of
preterm delivery.
2. Bacterial vaginosis may cause plasma-cell
endometritis, postpartum fever, post-hysterec-
tomy vaginal-cuff cellulitis, and postabortal infec-
tion.
3. Bacterial vaginosis is a risk factor for HIV acquisi-
tion and transmission.
E. Diagnosis. Three of the four criteria listed below
are necessary for diagnosis.
1. Homogeneous, grayish-white discharge
2. Vaginal pH >4.5
3. Positive whiff-amine test, defined as the pres-
ence of a fishy odor when 10% KOH is added to
vaginal discharge samples
4. Clue cells on saline wet mount (epithelial cells
studded with coccobacilli)
F. Therapy. Treatment is indicated in women with
symptomatic infection and those with asymptomatic
infection prior to abortion or hysterectomy.
1. Metronidazole or clindamycin administered either
orally or intravaginally will result in a high rate of
clinical cure (70-80%). Oral medication is more
convenient.
2. The oral regimen is 500 mg twice daily for 7
days. Topical vaginal therapy with 0.75%
metronidazole gel (MetroGel, 5 g once daily for 5
days) is as effective as oral metronidazole.
3. Single-dose therapy with 2 g of metronidazole
achieves a similar immediate rate of clinical re-
sponse.
4. Side effects of metronidazole include a metallic
taste, nausea, a disulfiram-like effect with alco-
hol, interaction with warfarin, and peripheral neu-
ropathy.
G. Relapse
1. Approximately 30% of patients have a recurrence
within three months. Recurrence usually reflects
a failure to eradicate the offending organisms.
Management of symptomatic relapse includes
prolonged therapy for 10 to 14 days.
2. Most women with a history of recurrent infection
benefit from suppressive therapy with
metronidazole gel 0.75% for 10 days, followed by
twice-weekly applications for three to six months.
V. Candida vulvovaginitis
A. Incidence. Candida vulvovaginitis accounts for one-
third of vaginitis. Up to 75% of women report having
had at least one episode of candidiasis. The condi-
tion is rare before menarche. It is less common in
postmenopausal women, unless they are taking
estrogen replacement therapy.
B. Microbiology and risk factors. Candida albicans
is responsible for 80-92% of vulvovaginal
candidiasis.
1. Antibiotics. A minority of women are prone to
vulvovaginal candidiasis while taking antibiotics.
2. Intrauterine devices have been associated with
vulvovaginal candidiasis.
3. Pregnancy. Symptomatic infection is more com-
mon in pregnancy.
C. Clinical features. Vulvar pruritus is the dominant
feature. Women may also complain of dysuria (ex-
ternal rather than urethral), soreness, irritation, and
dyspareunia. There is often little or no discharge.
Physical examination often reveals erythema of the
vulva and vaginal mucosa. The discharge is thick,
adherent, and “cottage cheese-like.”
D. Diagnosis
1. The vaginal pH is typically 4 to 4.5, which distin-
guishes candidiasis from Trichomonas or bacte-
rial vaginosis. The diagnosis is confirmed by
finding the organism on a wet mount; adding
10% potassium hydroxide facilitates recognition
of budding yeast and hyphae. Microscopy is neg-
ative in 50% of patients with vulvovaginal
candidiasis.
2. Empiric therapy is often considered in women
with typical clinical features, a normal vaginal pH,
and no other pathogens visible on microscopy.
Culture should be performed in patients with
persistent or recurrent symptoms.
E. Therapy
1. Women with mild infection usually respond to
treatment within a couple of days. More severe
infections require a longer course of therapy and
may take up to 14 days to fully resolve.
2. Uncomplicated infection. Both oral and topical
antimycotic drugs achieve comparable clinical
cure rates that are in excess of 80%.
3. Oral azole agents are more convenient. Side
effects of single-dose fluconazole (150 mg) tend
to be mild and infrequent, including gastrointesti-
nal intolerance, headache, and rash.

Treatment regimens for yeast vaginitis*

1-day regimens
Clotrimazole vaginal tablets (Mycelex G), 500 mg hs**
Fluconazole tablets (Diflucan), 150 mg PO
Itraconazole capsules (Sporanox), 200 mg PO bid
Tioconazole 6.5% vaginal ointment (Vagistat-1), 4.6 g hs** [5
g]

3-day regimens
Butoconazole nitrate 2% vaginal cream (Femstat 3), 5 g hs
[28 g]
Clotrimazole vaginal inserts (Gyne-Lotrimin 3), 200 mg hs**
Miconazole vaginal suppositories (Monistat 3), 200 mg hs**
Terconazole 0.8% vaginal cream (Terazol 3), 5 g hs
Terconazole vaginal suppositories (Terazol 3), 80 mg hs
Itraconazole capsules (Sporanox), 200 mg PO qd

5-day regimen
Ketoconazole tablets (Nizoral), 400 mg PO bid

7-day regimens
Clotrimazole 1% cream (Gyne-Lotrimin, Mycelex-7, Sweet'n
Fresh Clotrimazole-7), 5 g hs**
Clotrimazole vaginal tablets (Gyne-Lotrimin, Mycelex-7,
Sweet'n Fresh Clotrimazole-7), 100 mg hs**
Miconazole 2% vaginal cream (Femizol-M, Monistat 7), 5 g
hs**
Miconazole vaginal suppositories (Monistat 7), 100 mg hs**
Terconazole 0.4% vaginal cream (Terazol 7), 5 g hs

14-day regimens
Nystatin vaginal tablets (Mycostatin), 100,000 U hs

*Suppositories can be used if inflammation is predominantly

vaginal; creams if vulvar; a combination if both. Cream-sup-
pository combination packs available: clotrimazole (Gyne-
Lotrimin, Mycelex); miconazole (Monistat, M-Zole). Use 1-day
or 3-day regimen if compliance is an issue. Miconazole nitrate
may be used during pregnancy.

**Nonprescription formulation. If nonprescription therapies

fail, use terconazole 0.4% cream or 80-mg suppositories at
bedtime for 7 days.

4. Complicated infections. Factors that predis-

pose to complicated infection include uncon-
trolled diabetes, immunosuppression, and a his-
tory of recurrent vulvovaginal candidiasis.
Women with severe inflammation or complicated
infection require seven to 14 days of topical ther-
apy or two doses of oral therapy 72 hours apart.

Management options for complicated or recur-

rent yeast vaginitis

Extend any 7-day regimen to 10 to 14 days

Eliminate use of nylon or tight-fitting clothing
Consider discontinuing oral contraceptives
Consider eating 8 oz yogurt (with Lactobacillus acidophilus
culture) per day
Improve glycemic control in diabetic patients
For long-term suppression of recurrent vaginitis, use
ketoconazole, 100 mg (½ of 200-mg tablet) qd for 6 months

5. Partner treatment is not necessary since this is

not a primary route of transmission.
6. Pregnancy. Topical azoles applied for seven
days are recommended for treatment during
pregnancy.
VI. Trichomoniasis
A. Trichomoniasis, the third most common cause of
vaginitis, is caused by the flagellated protozoan,
Trichomonas vaginalis. The disorder is virtually
always sexually transmitted.
B. Clinical features. Trichomoniasis in women
ranges from an asymptomatic state to a severe,
acute, inflammatory disease. Signs and symptoms
include a purulent, malodorous, thin discharge
(70%) with associated burning, pruritus, dysuria,
and dyspareunia. Physical examination reveals
erythema of the vulva and vaginal mucosa; the
classic green-yellow frothy discharge is observed
in 10-30%. Punctate hemorrhages may be visible
on the vagina and cervix in 2%.
C. Complications. Infection is associated with pre-
mature rupture of the membranes and prematurity;
however, treatment of asymptomatic infection has
not been shown to reduce these complications.
Trichomoniasis is a risk factor for development of
post-hysterectomy cellulitis. The infection facilitates
transmission of the human immunodeficiency virus.
D. Diagnosis
1. The presence of motile trichomonads on wet
mount is diagnostic of infection, but this occurs
in only 50-70% of cases. Other findings include
an elevated vaginal pH (>4.5) and an increase
in polymorphonuclear leukocytes on saline mi-
croscopy.
E. Culture on Diamond's medium has a high sensi-
tivity (95%) and specificity (>95%) and should be
considered in patients with elevated vaginal pH,
increased numbers of polymorphonuclear leuko-
cytes and an absence of motile trichomonads and
clue cells on wet mount.
F. The OSOM Trichomonas Rapid Test for
Trichomonas antigens has a sensitivity of 88.3%
and specificity of 98.8%. Results can be read in 10
minutes. The Affirm VP III Microbial Identification
System (Becton Dickinson) test uses a nucleic acid
probe and is read in 45 minutes.
G. Cervical cytology. Trichomonads are sometimes
reported on conventional Papanicolaou (Pap)
smears. Conventional Pap smears are inadequate
for diagnosis of trichomoniasis because this tech-
nique has a sensitivity of only 60 to 70% and false
positive results are common (at least 8%). Asymp-
tomatic women with trichomonads identified on
conventional Pap smear should be evaluated by
wet mount and should not be treated until the diag-
nosis is confirmed.
H. Treatment of asymptomatic women with tricho-
monads noted on liquid-based cervical cytology is
appropriate.
VII. Treatment of Trichomonas vaginitis
A. Nonpregnant women
1. The 5-nitroimidazole drugs (metronidazole or
tinidazole) are the only class of drugs that pro-
vide curative therapy of trichomoniasis. Cure
rates are 90 to 95%.
2. Treatment consists of a single oral dose of 2
grams (four 500 mg tablets) of either tinidazole
(Fasigyn) or metronidazole (Flagyl). Cure rates
with tinidazole are comparable to those of
metronidazole, but better tolerated.
3. Similar cure rates are obtained with single and
multiple dose regimens (82 to 88%). Side ef-
fects (eg, nausea, vomiting, headache, metallic
taste, dizziness) appear to be dose related and
occur less frequently with the lower doses of
multiple dose, prolonged therapy (eg,
metronidazole 500 mg twice daily for seven
days. There is no multiple dose regimen for
tinidazole).
4. Oral is preferred to vaginal therapy since sys-
temic administration achieves therapeutic drug
levels in the urethra and periurethral glands.
5. Patients should be advised to not consume al-
cohol for 24 hours after metronidazole treatment
and 72 hours after tinidazole treatment because
of the possibility of a disulfiram-like (Antabuse
effect) reaction.
6. Follow-up is unnecessary for women who be-
come asymptomatic after treatment.
B. Male partners. T vaginalis infection in men is often
asymptomatic and transient (spontaneous resolu-
tion within 10 days). Symptoms, when present,
consist of a clear or mucopurulent urethral dis-
charge and/or dysuria. Complications include pros-
tatitis, balanoposthitis, epididymitis, and infertility.
Maximal cure rates are achieved when sexual
partners are treated simultaneously with the af-
 fected woman. Neither partner should resume
intercourse until both partners have completed
treatment, otherwise reinfection can occur.
C. Pregnancy
1. Metronidazole is the drug of choice for treatment
of symptomatic trichomoniasis in pregnancy.
Meta-analysis has not found any relationship
between metronidazole exposure during the first
trimester of pregnancy and birth defects. The
Centers for Disease Control and Prevention no
longer discourage the use of metronidazole in
the first trimester.
2. In pregnant women, some clinicians prefer
metronidazole 500 mg twice daily for five to
seven days to the 2 g single dose regimen be-
cause of the lower frequency of side effects.
3. Asymptomatic infections during pregnancy
should not be treated because treatment does
not prevent, and may even increase, the risk of
preterm delivery.

Treatment options for trichomoniasis

Initial measures
Tinidazole (Fasigyn) 2 g PO in a single dose. Cure rates with
tinidazole are comparable to those of metronidazole, but
better tolerated.
Metronidazole (Flagyl, Protostat), 2 g PO in a single dose, or
metronidazole, 500 mg PO bid X 7 days, or metronidazole,
375 mg PO bid X 7 days
Treat male sexual partners

Measures for treatment failure

Treatment sexual contacts
Re-treat with tinazole 2 gm PO or metronidazole, 500 mg PO
bid X 7 days
If infection persists, confirm with culture and re-treat with
metronidazole,
2-4 g PO qd X 3-10 days

VIII. Other causes of vaginitis and vaginal discharge

A. Atrophic vaginitis
1. Reduced endogenous estrogen causes thinning
of the vaginal epithelium. Symptoms include
vaginal soreness, postcoital burning, dyspare-
unia, and spotting. The vaginal mucosa is thin
with diffuse erythema, occasional petechiae or
ecchymoses, and few or no vaginal folds. There
may be a serosanguineous or watery discharge
with a pH of 5.0-7.0.
2. Treatment consists of topical vaginal estrogen.
Vaginal ring estradiol (Estring), a silastic ring
impregnated with estradiol, is the preferred
means of delivering estrogen to the vagina. The
silastic ring delivers 6 to 9 µg of estradiol to the
vagina daily. The rings are changed once every
three months. Concomitant progestin therapy is
not necessary.
3. Conjugated estrogens (Premarin), 0.5 gm of
cream, or one-eighth of an applicatorful daily
into the vagina for three weeks, followed by
twice weekly thereafter is also effective. Con-
comitant progestin therapy is not necessary.
4. Estrace cream (estradiol) can also by given by
vaginal applicator at a dose of one-eighth of an
applicator or 0.5 g (which contains 50 µg of
estradiol) daily into the vagina for three weeks,
followed by twice weekly thereafter. Concomi-
tant progestin therapy is not necessary.
5. Oral estrogen (Premarin) 0.3 mg qd should
also provide relief.
B. Desquamative inflammatory vaginitis
1. Chronic purulent vaginitis usually occurs
perimenopausally, with diffuse exudative vagini-
tis, massive vaginal-cell exfoliation, purulent
vaginal discharge, and occasional vaginal and
cervical spotted rash.
2. Laboratory findings included an elevated pH,
increased numbers of parabasal cells, the ab-
sence of gram-positive bacilli and their replace-
ment by gram-positive cocci on Gram staining.
Clindamycin 2% cream is usually effective.
C. Noninfectious vaginitis and vulvitis
1. Noninfectious causes of vaginitis include irri-
tants (eg, minipads, spermicides, povidone-io-
dine, topical antimycotic drugs, soaps and per-
fumes) and contact dermatitis (eg, latex con-
doms and antimycotic creams).
2. Typical symptoms include pruritus, irritation,
burning, soreness, and variable discharge. The
diagnosis should be suspected in symptomatic
women who do not have an otherwise apparent
infectious cause.
3. Management of noninfectious vaginitis includes
identifying and eliminating the offending agent.
Sodium bicarbonate sitz baths and topical vege-
table oils. Topical corticosteroids are not recom-
mended.
References: See page 208.

Trichomonas Vaginitis
Trichomonas vaginalis is the causative agent of
trichomoniasis, accounting for 35% of vaginitis. The
prevalence of trichomoniasis in black, white, and
Mexican-American women is 13.5, 1.2, and 1.5%, re-
spectively.

I. Microbiology and risk factors

A. Trichomonas is a flagellated protozoan, which
may be found in the vagina, urethra, paraurethral
glands, and Bartholins and Skene's glands.
B. Trichomoniasis is virtually always sexually trans-
mitted, although survival on fomites has been
reported. It is associated with a high prevalence of
coinfection with other sexually transmitted dis-
eases.
II. Clinical features
A. Trichomoniasis in women ranges from an asymp-
tomatic carrier state to a severe, acute, inflamma-
tory disease.
B. Signs and symptoms include a purulent, mal-
odorous, thin discharge (70% of cases) with burn-
ing, pruritus, dysuria, frequency, and dyspareunia.
Postcoital bleeding can occur. The urethra is also
infected in the majority of women.
C. Physical examination often reveals erythema of
the vulva and vaginal mucosa; green-yellow frothy
discharge is observed in 10 to 30%. Punctate
hemorrhages may be visible on the vagina and
cervix ("strawberry cervix") in 2%.

Clinical Features of Vaginitis

Vulvovagi Bacte-
Var No nal rial
iab rm Trichomoniasis
candidiasi vaginos
le al s is
Mal-
Pruritus, odorous
Sy soreness, dis- Malodorous, pu-
mp No change in charge, rulent discharge,
to ne discharge, no dyspareunia
ms dyspareuni dyspare
a unia
Vulvar ery- Purulent dis-
Adher-
Sig thema, charge,
- ent dis-
ns edema, vulvovaginal ery-
charge
fissure thema
4.
pH 0- 4.0-4.5 >4.5 5.0-6.0
4.5
PM
N:E
C
rati PMN:EC PMN:EC
o ratio <1; <1; loss
Sal <1; rods domi- of rods;
ine rod PMN ++++;
nate; in-
mic s mixed flora;
squames creased
ros do motile tricho-
+++; coccoba
cop min monads (60%)
pseudohyp cilli; clue
y ate; hae (about cells
squ 40%) (>90%)
am
es
++
+
10
%
pot
ass
ium Pseudohy
Ne
hyd phae Nega-
gati Negative
roxi (about tive
ve
de 70%)
exa
min
atio
n
Mis Culture if
cell Culture
micros- Culture if micros-
an - of no
copy nega- copy negative
eo value
tive
us
Contact Purulent vagini-
Diff Ph irritant or tis,
ere ysi allergic desquamative
ntia olo vulvitis, inflammatory
l gic chemical vaginitis, atro-
dia leu irritation, phic vaginitis
gn kor focal plus secondary
osi rhe vulvitis infection, erosive
s a (vulvodyni lichen planus
a)

III. Complications
A. Trichomoniasis is a risk factor for post-hysterec-
tomy cellulitis, tubal infertility, and cervical neo-
plasia. Infection facilitates transmission of the
human immunodeficiency virus (HIV).
B. Trichomoniasis in pregnancy is associated
with premature rupture of the membranes and
preterm delivery; however, treatment of asymp-
tomatic infection has not been shown to reduce
these complications.
IV. Diagnosis
A. Microscopy and pH. The presence of motile
trichomonads on wet mount is diagnostic of infec-
tion, but this occurs in only 50 to 70% of cases.
Other findings include an elevated vaginal pH
(>4.5) and an increase in polymorphonuclear
leukocytes.
B. Culture on Diamond's medium has a high sen-
sitivity (95%) and specificity (>95%) and should
be considered in patients with elevated vaginal
pH, increased numbers of polymorphonuclear
leukocytes and an absence of motile tricho-
monads and clue cells on wet mount.
C. OSOM Trichomonas Rapid Test for
Trichomonas antigens has a sensitivity of
88.3% and specificity of 98.8%. Results can be
read in 10 minutes. The Affirm VP III Microbial
Identification System (Becton Dickinson) test
uses a nucleic acid probe and is read in 45 min-
utes.
D. Cervical cytology. Trichomonads are some-
times reported on Papanicolaou (Pap) smears.
Pap smears are inadequate for diagnosis of
trichomoniasis because this technique has a
sensitivity of only 60 to 70% and false positive
results are common (at least 8%). Asymptomatic
women with trichomonads identified on conven-
tional Pap smear should be evaluated by wet
mount and should not be treated until the diagno-
sis is confirmed.
E. Treatment of asymptomatic women with tricho-
monads noted on liquid-based cervical cytology
is appropriate.
V. Treatment of Trichomonas vaginitis
A. Nonpregnant women
1. The 5-nitroimidazole drugs (metronidazole or
tinidazole) are the only class of drugs that
provide curative therapy of trichomoniasis.
Cure rates are 90 to 95%.
2. Treatment consists of a single oral dose of 2
grams (four 500 mg tablets) of either
tinidazole or metronidazole. Cure rates with
tinidazole are comparable to those of
metronidazole, but better tolerated.
3. Similar cure rates are obtained with single and
multiple dose regimens (82 to 88%). Side ef-
fects (eg, nausea, vomiting, headache, metal-
lic taste, dizziness) appear to be dose related
and occur less frequently with the lower doses
of multiple dose, prolonged therapy (eg,
metronidazole 500 mg twice daily for seven
days. There is no multiple dose regimen for
tinidazole).
4. Oral is preferred to vaginal therapy since sys-
temic administration achieves therapeutic drug
levels in the urethra and periurethral glands.
5. Patients should be advised to not consume
alcohol for 24 hours after metronidazole treat-
ment and 72 hours after tinidazole treatment
because of the possibility of a disulfiram-like
(Antabuse effect) reaction.
6. Follow-up is unnecessary for women who be-
come asymptomatic after treatment.
B. Male partners. T vaginalis infection in men is
often asymptomatic and transient. Symptoms,
when present, consist of a clear or mucopurulent
urethral discharge and/or dysuria. Complications
include prostatitis, balanoposthitis, epididymitis,
and infertility. Maximal cure rates are achieved
when sexual partners are treated simultaneously
with the affected woman. Neither partner should
resume intercourse until both partners have com-
pleted treatment
C. Pregnancy
 1. Metronidazole is the drug of choice for treat-
ment of symptomatic trichomoniasis in preg-
nancy.
2. In pregnant women, some clinicians prefer
metronidazole 500 mg twice daily for five to
seven days to the 2 g single dose regimen
because of the lower frequency of side effects.
3. Asymptomatic infections during pregnancy
should not be treated because treatment does
not prevent, and may even increase, the risk
of preterm delivery.
References: See page 208.

Gynecologic Oncology
Cervical Cancer

Invasive cervical carcinoma is the third most common

cancer in the United States. The International Federation
of Gynecology and Obstetrics (FIGO) recently revised its
staging criteria. Survival rates for women with cervical
cancer improve when radiotherapy is combined with
cisplatin-based chemotherapy.

I. Clinical evaluation
A. Human papillomavirus is the most important factor
contributing to the development of cervical
intraepithelial neoplasia and cervical cancer. Other
epidemiologic risk factors associated with cervical
intraepithelial neoplasia and cervical cancer in-
clude history of sexual intercourse at an early age,
multiple sexual partners, sexually transmitted dis-
eases (including chlamydia), and smoking. Addi-
tional risk factors include a male partner or part-
ners who have had multiple sexual partners; previ-
ous history of squamous dysplasias of the cervix,
vagina, or vulva; and immunosuppression.
B. The signs and symptoms of early cervical carci-
noma include watery vaginal discharge, intermit-
tent spotting, and postcoital bleeding. Diagnosis
often can be made with cytologic screening,
colposcopically directed biopsy, or biopsy of a
gross or palpable lesion. In cases of suspected
microinvasion and early-stage cervical carcinoma,
cone biopsy of the cervix is indicated to evaluate
the possibility of invasion or to define the depth
and extent of microinvasion. Cold knife cone bi-
opsy provides the most accurate evaluation of the
margins.
C. Histology. The two major histologic types of inva-
sive cervical carcinomas are squamous cell carci-
nomas and adenocarcinomas. Squamous cell
carcinomas comprise 80% of cases, and
adenocarcinoma or adenosquamous carcinoma
comprise approximately 15%.
II. Staging of cervical cancer
A. Histologic confirmation of invasive cervical cancer
should be followed by a careful staging evaluation.
B. Physical examination. The cervix and entire va-
gina should be carefully inspected and palpated to
identify overt tumors or subepithelial vaginal exten-
sion. Rectovaginal examination permits the best
clinical assessment of tumor size and parametrial
involvement. Palpation of the right upper quadrant
and inguinal and supraclavicular lymph nodes is
important to screen for metastatic disease.
C. Laboratory studies. Laboratory studies should
include a complete blood count and renal and liver
function tests.

Pretreatment Assessment of Women with

Histologic Diagnosis of Cervical Cancer

History
Physical examination
Complete blood count, blood urea nitrogen, creatinine, hepatic
function
Chest radiography
Intravenous pyelography or computed tomography of abdo-
men with intravenous contrast
Consider the following: barium enema, cystoscopy,
rectosigmoidoscopy

Staging of Carcinoma of the Cervix Uteri: FIGO

Nomenclature

Stage 0 Carcinoma in situ, cervical intraepithelial neoplasia

Grade III

Stage I The carcinoma is strictly confined to the cervix (ex-

tension to the corpus would be disregarded).

la Invasive carcinoma that can be diagnosed only by

microscopy. All macroscopically visible lesions-
even with superficial invasion-are allotted to Stage
Ib carcinomas. Invasion is limited to a measured
stromal invasion with a maximal depth of 5.0 mm
and a horizontal extension of not more than 7.0
mm. Depth of invasion should not be more than
5.0 mm taken from the base of the epithelium of
the original tissue-superficial or glandular. The
involvement of vascular spaces-venous or
lymphatic-should not change the stage allotment.
la1 Measured stromal invasion of not more
than 3.0 mm in depth and extension of
not more than 7.0 mm
Ia2 Measured stromal invasion of more than
3.0 mm and not more than 5.0 mm with
an extension of not more than 7.0 mm
Ib Clinically visible lesions limited to the cervix uteri
or preclinical cancers greater than Stage la
Ib1 Clinically visible lesions not more than 4.0
cm
Ib2 Clinically visible lesions more than 4.0 cm

Stage II Cervical carcinoma invades beyond the uterus, but

not to the pelvic wall or to the lower third of the
vagina

Ila No obvious parametrial involvement

IIb Obvious parametrial involvement

Stage III The carcinoma has extended to the pelvic wall. On

rectal examination, there is no cancer-free space between
the tumor and the pelvic wall. The tumor involves the lower
third of the vagina. All cases with hydronephrosis or
nonfunctioning kidney are included, unless they are known to
be due to other causes.
IIIa Tumor involves lower third of the vagina, with no
extension to the pelvic wall
IIIb Extension to the pelvic wall or hydronephrosis or
nonfunctioning kidney

Stage IV The carcinoma has extended beyond the true pel-

vis, or has involved (biopsy proved) the mucosa of
the bladder or rectum. Bullous edema, as such,
does not permit a case to be allotted to Stage IV.
IVa Spread of the growth to adjacent organs (bladder
or rectum or both)
IVb Spread to distant organs

Guidelines for Clinical Staging of Invasive Cervi-

cal Carcinoma

Examinations should include inspection, palpation,

colposcopy, endocervical curettage, hysteroscopy,
cystoscopy, proctoscopy, intravenous pyelography, and X-ray
examination of lungs and skeleton.

Conization of the cervix is considered a clinical examination.

Suspected bladder or rectal involvement should be confirmed

histologically.

If there is a question about the most appropriate stage, the

earlier stage should be assigned.

III. FIGO staging systems

A. The International Federation of Gynecologists and
Obstetricians (FIGO) staging system is based
upon clinical evaluation. This examination should
be performed under anesthesia whenever neces-
sary.
B. Based upon FIGO guidelines, the following exami-
nations are appropriate to establish the stage of
disease: palpation and inspection of the primary
tumor, palpation of groin and supraclavicular
lymph nodes, colposcopy, endocervical curettage,
conization, hysteroscopy, cystoscopy, proctoscopy,
intravenous pyelogram (IVP), and radiographic
examination of the lungs and skeleton.
C. Chest X-rays are indicated in all patients with cer-
vical cancer, and imaging of the urinary tract (IVP,
magnetic resonance or computed tomography
urogram) should be carried out in all patients with
more than microscopic cervical cancer. Suspected
rectal or bladder involvement requires confirmation
by biopsy.
IV. Optional evaluation procedures. Although they are
not used to assign disease stage in the FIGO classi-
fication, optional staging examinations, including
computed tomography (CT), magnetic resonance
imaging (MRI), positron emission tomography (PET),
lymphangiography, ultrasonography, or laparoscopy,
may be of value for planning treatment, particularly
the extent of the radiation therapy (RT) field or scope
of surgery.
A. MRI is the preferred modality to provide informa-
tion about tumor size, degree of stromal penetra-
tion, nodal metastasis, and local tissue exten-
sion. Positive findings should be histologically
confirmed by fine needle aspiration under CT
guidance.
V. Surgical evaluation. Although cervical cancer is
staged clinically, the results of surgical staging can
be used for treatment planning. The staging proce-
dure can be performed through a laparotomy
(transperitoneal or extraperitoneal) or
laparoscopically. Surgical staging allows for a com-
plete pelvic and paraaortic lymphadenectomy. Nodal
tissue obtained at the time of surgery can detect
microscopic disease. Staging offers an opportunity to
resect bulky metastatic lymph nodes and allows for
individualization of the radiation field. In
premenopausal women, oophoropexy can be done
at the same time to protect the ovaries from radiation
damage.
VI. Treatment of microinvasive cervical cancer. Ac-
cording to the FIGO criteria, patients with stage Ia 1
carcinoma could be treated with simple hysterectomy
without nodal dissection or conization in selected
cases. Those patients with invasion >3 mm and no
greater than 5 mm (stage Ia2) should undergo radi-
cal hysterectomy and pelvic lymphadenectomy. Al-
though lymphatic-vascular invasion should not alter
the FIGO stage, it is an important factor in treatment
decisions. The risk of recurrence with lymphatic-
vascular involvement is 3.1% if the extent of invasion
is 3 mm or less and 15.7% if it is greater than 3 mm
and no greater than 5 mm. Therefore, the presence
of lymphatic-vascular invasion would suggest the
need for more radical treatment.
VII. Treatment of early-stage (Ib-lla) carcinoma
A. Both treatment strategies for stage Ib and early-
stage IIa invasive carcinoma include 1) a primary
surgical approach with radical hysterectomy and
pelvic lymphadenectomy or 2) primary radiation
therapy with external beam radiation and either
high-dose-rate or low-dose-rate brachytherapy.
The 5-year survival rate is 87-92% using either
approach.
B. Radical surgery leaves the vagina in more func-
tional condition, while radiation therapy results in
a reduction in length, caliber, and lubrication of
the vagina. In premenopausal women, ovarian
function can be preserved with surgery. The sur-
gical approach also provides the opportunity for
pelvic and abdominal exploration and provides
better clinical and pathologic information with
which to individualize treatment.
VIII. Adjuvant therapy following primary surgery in
early-stage carcinoma
A. Patients with histologically documented
extracervical disease (pelvic nodal involvement,
positive margins, or parametrial extension) are
treated with concurrent pelvic radiation therapy
and cisplatin-based chemotherapy. The use of
combined adjuvant chemotherapy and radiation
therapy in these high-risk patients following pri-
mary surgery significantly improves relapse-free
survival and overall survival rates when com-
pared with radiation therapy alone.
B. Following radical hysterectomy, a subset of node-
negative patients who have a constellation of
primary risk factors (large tumors, depth of
stromal infiltration, and lymphovascular space
involvement) may be defined as having interme-
diate risk for relapse. For these patients,
adjuvant pelvic radiation therapy provides clear
therapeutic benefit, with significantly improved
relapse-free survival rates when compared with
those who had no further therapy.
IX. Treatment of late-stage carcinoma (lIb or later).
Cisplatin is usually administered weekly as a single
agent because of its ease of delivery and favorable
toxicity profile. Women with locally advanced cervical
cancer in North America should receive cisplatin-
based chemotherapy concurrent with radiation ther-
apy.
X. Long term monitoring. Approximately 35% of pa-
tients will have persistent or recurrent disease. A
common approach includes examinations and Pap
tests every 3-4 months for the first 3 years, decreas-
ing to twice yearly in the fourth and fifth years, with
and chest X-rays annually for up to 5 years.
References: See page 208.
Endometrial Cancer
Uterine cancer is the most common malignant neoplasm
of the female genital tract and the fourth most common
cancer in women. About 6,000 women in the United
States die of this disease each year. It is more frequent
in affluent and white, especially obese, postmenopausal
women of low parity. Hypertension and diabetes mellitus
are also predisposing factors.

I. Risk factors
A. Any characteristic that increases exposure to un-
opposed estrogen increases the risk for
endometrial cancer. Conversely, decreasing expo-
sure to estrogen limits the risk. Unopposed estro-
gen therapy, obesity, anovulatory cycles and
estrogen-secreting neoplasms all increase the
amount of unopposed estrogen and thereby in-
crease the risk for endometrial cancer. Smoking
seems to decrease estrogen exposure, thereby
decreasing the cancer risk, and oral contraceptive
use increases progestin levels, thus providing pro-
tection.

Risk Factors for Endometrial Cancer

Unopposed estrogen exposure
Median age at diagnosis: 59 years
Menstrual cycle irregularities, specifically menorrhagia and
menometrorrhagia
Postmenopausal bleeding
Chronic anovulation
Nulliparity
Early menarche (before 12 years of age)
Late menopause (after 52 years of age)
Infertility
Tamoxifen (Nolvadex) use
Granulosa and thecal cell tumors
Ovarian dysfunction
Obesity
Diabetes mellitus
Arterial hypertension with or without atherosclerotic heart
disease
History of breast or colon cancer

B. Hormone replacement therapy. Unopposed es-

trogen treatment of menopause is associated with
an eightfold increased incidence of endometrial
cancer. The addition of progestin decreases this
risk dramatically.
II. Clinical evaluation
A. Ninety% of patients with endometrial cancer have
abnormal vaginal bleeding, usually presenting as
menometrorrhagia in a perimenopausal woman or
menstrual-like bleeding in a woman past meno-
pause. Perimenopausal women relate a history of
intermenstrual bleeding, excessive bleeding last-
ing longer than seven days or an interval of less
than 21 days between menses. Heavy, prolonged
bleeding in patients known to be at risk for
anovulatory cycles should prompt histologic evalu-
ation of the endometrium. The size, contour, mo-
bility and position of the uterus should be noted.
B. Patients who report abnormal vaginal bleeding and
have risk factors for endometrial cancer should
have histologic evaluation of the endometrium.
Premenopausal patients with amenorrhea for more
than six to 12 months should be offered
endometrial sampling, especially if they have risk
factors associated with excessive estrogen expo-
sure. Postmenopausal women with vaginal bleed-
ing who either are not on hormonal replacement
therapy or have been on therapy longer than six
months should be evaluated by endometrial sam-
pling.
C. Endometrial sampling
1. In-office sampling of the endometrial lining may
be accomplished with a Novak or Kevorkian
curet, the Pipelle endometrial-suction curet, or
the Vabra aspirator. Before having an in-office
biopsy, the patient should take a preoperative
dose of a nonsteroidal anti-inflammatory drug
(NSAID). With the patient in the lithotomy posi-
tion, a speculum is inserted in the vaginal canal.
The cervix should be cleansed with a small
amount of an antiseptic solution. After 1 mL of a
local anesthetic is infused into the anterior lip of
the cervix, a tenaculum is placed. The
paracervical block is then performed using 1 or
2% lidocaine (Xylocaine) without epinephrine.
2. The cannula is then placed in the uterus and
placement is confirmed with the help of the
centimeter markings along the cannula. The
inner sleeve is then pulled back while the can-
nula is held within the cavity. This generates a
vacuum in the cannula that can be used to col-
lect endometrial tissue for diagnosis. Moving
the cannula in and out of the cavity no more
than 2 to 3 cm with each stroke while turning
the cannula clockwise or counterclockwise is
helpful in obtaining specimens from the entire
cavity.
III. Treatment of endometrial cancer
A. The treatment of endometrial cancer is usually
surgical, such as total abdominal hysterectomy,
bilateral salpingo-oophorectomy and evaluation for
metastatic disease, which may include pelvic or
para-aortic lymphadenectomy, peritoneal cytologic
examination and peritoneal biopsies. The extent of
the surgical procedure is based on the stage of
disease, which can be determined only at the time
of the operation.

Staging for Carcinoma of the Corpus Uteri

Stage* Description

IA (G1, G2, G3) Tumor limited to endometrium

IB (G1, G2, G3) Invasion of less than one half of the

myometrium

IC (G1, G2, G3) Invasion of more than one half of the

myometrium

IIA (G1, G2, G3) Endocervical gland involvement

IIB (G1, G2, G3) Cervical stromal involvement

IIIA (G1, G2, Invasion of serosa and/or adnexa

G3) and/or positive peritoneal cytologic
results

IIIB (G1, G2, Metastases to vagina

G3)

IIIC (G1, G2, Metastases to pelvic and/or para-aor-

G3) tic lymph nodes

IVA (G1, G2, Invasion of bladder and/or bowel mu-

G3) cosa

IVB Distant metastases including intra-

abdominal and/or inguinal lymph
nodes

*--Carcinoma of the corpus is graded (G) according to the

degree of histologic differentiation: G1 = 5% or less of a
solid growth pattern; G2 = 6 to 50% of a solid growth pat-
tern; G3 = more than 50% of a solid growth pattern.

B. For most patients whose cancers have progressed

beyond stage IB grade 2, postoperative radiation
therapy is recommended. Because tumor re-
sponse to cytotoxic chemotherapy has been poor,
chemotherapy is used only for palliation.
C. Endometrial hyperplasia with atypia should be
treated with hysterectomy except in extraordinary
cases. Progestin treatment is a possibility in
women younger than 40 years of age who refuse
hysterectomy or who wish to retain their childbear-
ing potential, but an endometrial biopsy should be
performed every three months. Treatment of atypi-
cal hyperplasia and well-differentiated endometrial
cancer with progestins in women younger than 40
years of age results in complete regression of
disease in 94% and 75%, respectively.
D. Patients found to have hyperplasia without atypia
should be treated with progestins and have an
endometrial biopsy every three to six months.
IV. Serous and clear cell adenocarcinomas
A. These cancers are considered in a separate cate-
gory from endometrioid adenocarcinomas. They
have a worse prognosis overall. Patients with seri-
ous carcinomas have a poorer survival. The 3 year
survival is 40% for stage I disease.
B. Serous and clear cell carcinomas are staged like
ovarian cancer. A total abdominal hysterectomy
and bilateral salpingo-oophorectomy, lymph node
biopsy, and omental biopsy/omentectomy are
completed. Washings from the pelvis, gutters and
diaphragm are obtained, and the diaphragm is
sampled and peritoneal biopsies completed.
References: See page 208.

Ovarian Cancer
Ovarian cancer is the second most common gynecologic
malignancy, but the most common cause of death
among women who develop gynecologic cancer, and it
is the fifth most common cancer in females. The majority
(90%) of primary ovarian tumors derive from epithelial
cells, although they can also arise from germ cell tu-
mors, sex cord-stromal tumors, and mixed cell type
tumors.

I. Clinical manifestations
A. Most ovarian cancers are diagnosed between the
ages of 40 and 65. Symptoms of early stage dis-
ease are often vague. Acute symptoms due to
ovarian rupture or torsion are unusual. As a result,
75 to 85% of cases of ovarian cancer are ad-
vanced at the time of diagnosis. More advanced
disease is typically associated with abdominal
distention, nausea, anorexia, or early satiety due
to the presence of ascites and omental or bowel
metastases.
B. Most women have nonspecific symptoms, such as
lower abdominal discomfort or pressure, gas,
bloating, constipation, irregular menstrual cy-
cles/abnormal vaginal bleeding, low-back pain,
fatigue, nausea, indigestion, urinary frequency, or
dyspareunia.
II. Physical examination
A. Palpation of an asymptomatic adnexal mass dur-
ing a routine pelvic examination is the usual pre-
sentation for ovarian cancer. The presence of a
solid, irregular, fixed pelvic mass on pelvic exami-
nation is highly suggestive of an ovarian malig-
nancy. However, endometriomas and tubo-ovar-
ian abscesses are benign tumors that may be
fixed, while cystadenofibromas and tubo-ovarian
abscesses are benign masses that feel irregular.
The diagnosis of malignancy is almost certain if a
fixed, irregular pelvic mass is associated with an
upper abdominal mass or ascites.

Differential Diagnosis of Adnexal Masses in

Women

Extraovarian mass Pedunculated fibroid

Ectopic pregnancy Diverticular abscess
Hydosalpinx or Appendiceal abscess
tuboovarian abscess
Paraovarian cyst
Peritoneal inclusion cyst

Ovarian mass Theca lutein cysts

Simple or hemorrhagic
physiologic cysts (eg,
follicular, corpus luteum)
Endometrioma
Benign or malignant
neoplasms (eg, epithe-
lial, germ cell, sex-cord)
Metastatic carcinoma
(eg, breast, colon,
endometrium)

III. Diagnostic evaluation

A. The finding of a pelvic mass usually requires sur-
gery for definitive histologic diagnosis. Tumor
markers (eg, serum CA 125) and ultrasound ex-
amination can help distinguish between malignant
and benign pelvic masses.
B. A complete pelvic examination and assessment of
cervical cytology should be performed preopera-
tively. Routine hematologic and biochemical as-
sessments should be obtained prior to surgery.
Ultrasonography for diagnosis of ovarian malig-
nancy has a sensitivity of 62 to 100% and a speci-
ficity of 77 to 95%.
C. It is reasonable to pursue a period of observation
in a premenopausal woman with an adnexal mass
if the mass is not clinically suspicious on
ultrasonography. Adnexal masses that are mobile,
purely cystic, unilateral, less than 8 to 10 cm in
diameter, and have smooth internal and external
contours by ultrasound are highly unlikely to be
malignant and can be followed for two months;
the majority of physiologic cysts will regress dur-
ing this time.
D. Exploration is indicated if there is no resolution
within two months. However, women who have
solid, fixed, irregularly shaped, or large masses
should undergo surgery. A mass that increases in
 size or does not regress must be presumed to be
neoplastic and should be removed surgically.
E. The threshold for surgical intervention is lower in
postmenopausal women; those with cysts >3 cm
should undergo exploratory surgery, laparotomy,
or laparoscopy.
F. Tumor markers. CA 125: The preoperative eval-
uation of a woman with suspected ovarian cancer
should include measurement of the CA 125 con-
centration. The serum CA 125 (normal <35 U/mL)
is elevated (>65 U/mL) in 80% of women with
epithelial ovarian cancer. It is also increased in
patients with other malignancies, including
endometrial cancer and certain pancreatic can-
cers; in endometriosis, uterine leiomyoma, and
pelvic inflammatory disease; and in approximately
1% of healthy women.
IV. Staging
A. Surgery is necessary for diagnosis, accurate stag-
ing and optimal cytoreduction, and is crucial for
the successful treatment of EOC. Ovarian malig-
nancies are surgically staged according to the
2002 revised American Joint Committee on Can-
cer (AJCC) and International Federation of
Gynecologic Oncologists (FIGO) joint staging
system, as long as the patient is an appropriate
surgical candidate.

Definitions of the Stages in Primary Carcinoma

of the Ovary

Sta Definition
ge

I Growth is limited to the ovaries

IA Growth is limited to one ovary; no ascites

present containing malignant cells; no tumor
on the external surface; capsule is intact
IB
Growth is limited to both ovaries; no ascites
present containing malignant cells; no tumor
IC on the external surfaces; capsules are intact

Tumor is classified as either stage IA or IB

but with tumor on the surface of one or both
ovaries; or with ruptured capsule(s); or with
ascites containing malignant cells present or
with positive peritoneal washings

II Growth involves one or both ovaries with

pelvic extension
IIA
Extension and/or metastases to the uterus
lIB and/or tubes
IIC Extension to other pelvic tissues

Tumor is either stage IIA or lIB but with tu-

mor on the surface of one or both ovaries; or
with capsule(s) ruptured; or with ascites con-
taining malignant cells present or with posi-
tive peritoneal washings

III Tumor involves one or both ovaries with

peritoneal implants outside the pelvis and/or
positive retroperitoneal or inguinal nodes;
superficial liver metastasis equals stage III;
IlIA tumor is limited to the true pelvis but with
histologically proven malignant extension to
small bowel or omentum
IIIB
Tumor is grossly limited to the true pelvis
with negative nodes but with histologically
IIIC confirmed microscopic seeding of abdominal
peritoneal surfaces

Tumor involves one or both ovaries with

histologically confirmed implants of abdomi-
nal peritoneal surfaces, none exceeding 2
cm in diameter; nodes are negative

Abdominal implants >2 cm in diameter

and/or positive retroperitoneal or inguinal
nodes

IV Growth involves one or both ovaries with

distant metastases; if pleural effusion is
present, there must be positive cytology
findings to assign a case to stage IV;
parenchymal liver metastasis equals stage
IV

B. Procedure
1. The staging procedure is usually approached
through a laparotomy incision. Any free fluid in
the cul-de-sac is submitted for cytologic evalu-
ation. Washings of the peritoneal cavity are
obtained by instilling and removing 50 to 100
mL of saline. The affected adnexa should be
removed intact and a frozen section obtained
to determine or confirm the diagnosis. Thor-
ough surgical staging should be carried out in
the absence of obvious stage IV disease.
Preservation of the uterus and a normal ap-
pearing contralateral adnexa is an option in
women desirous of maintaining future fertility.
2. All intraperitoneal surfaces should be carefully
inspected and suspicious areas or adhesions
should be biopsied. If there is no evidence of
disease, multiple intraperitoneal biopsies
should be performed, including from the cul-
de-sac, both gutters, bladder peritoneum, and
bowel mesentery.
3. The diaphragm is evaluated by either biopsy
or cytologic smear. A complete omentectomy
should be performed.
4. The retroperitoneal spaces are explored to
dissect the pelvic and paraaortic lymph nodes.
Any enlarged lymph nodes should be resected
and submitted separately for histopathologic
evaluation.
5. For patients with advanced disease, optimal
cytoreduction (debulking) should be attempted
at the time of initial surgery. The majority of
women with EOC (except for those with stage
I disease) will require surgery and chemother-
apy.
V. Treatment of ovarian cancer
A. Cytoreductive surgery improves response to
chemotherapy and survival of women with ad-
vanced ovarian cancer. Operative management
is designed to remove as much tumor as possi-
ble. When a malignant tumor is present, a thor-
ough abdominal exploration, total abdominal
hysterectomy, bilateral salpingo-oophorectomy,
lymphadenectomy, omentectomy, and removal of
all gross cancer are standard therapy.
B. Adjuvant therapy
1. Patients with stage IA or IB disease (who have
been completely surgically staged) and who
have borderline, well- or moderately differenti-
ated tumors do not benefit from additional
chemotherapy because their prognosis is ex-
cellent with surgery alone.
2. Chemotherapy improves survival and is an
effective means of palliation of ovarian cancer.
In patients who are at increased risk of recur-
rence (stage I G3 and all IC-IV), chemother-
apy is recommended. Sequential clinical trials
of chemotherapy agents demonstrate that
cisplatin (or carboplatin) given in combination
with paclitaxel is the most active combination
identified.
References: See page 208.

Breast Cancer
One of 8 women will develop breast cancer. The risk of
breast cancer increases with age; approximately half of
new cases occur in women aged 65 years or older.
Two% of 40- to 49-year-old women in the United States
develop breast cancer during the fifth decade of their
lives, and 0.3% die from breast cancer. Breast cancer is
the most common malignancy in American women, and
the second most lethal malignancy in women, following
lung cancer.

I. Risk Factors
A. Major risk factors for breast cancer include: 1)
early menarche, 2) nulliparity, 3) delayed childbirth,
4)increasing age, 5) race, and 6) family history.

Risk Factors for Breast Cancer

Major Risk Factors

Early menarche
Nulliparity
Delayed childbirth
Increasing age
Race
Family history

Other Risk Factors

Late menopause
Obesity
Weight gain
Increased intra-abdominal
fat (android body habitus)
Lack of regular exercise
Elevated serum estradiol
Elevated free testosterone
levels
A previous premalignant
breast biopsy
Radial scars in benign
breast biopsies
A history of breast cancer
Exposure to ionizing radia-
tion
Higher bone mineral density
Smoking
Alcohol consumption
Elevated insulin-like growth
factor- I (IGF- I) levels
Increased mammographic
density
Oral contraceptives

Familial Risk Factors for Breast Cancer

More than 50% of women in family have breast cancer
Breast cancer present in more than I generation
Multiple occurrences of breast cancer (>3) in close relatives
Onset at less than age 45 years
History of bilateral breast cancer
High rate of co-existing ovarian cancer
BRCA1 gene mutation

B. Nulliparity and increased age at first pregnancy

are associated with an increased risk for breast
cancer. Nulliparity alone accounts for 16% of new
cases of breast cancer each year. The relative
risk for breast cancer increases with advancing
age.
C. Race is an independent risk factor. While white
women are at an increased risk for breast cancer,
African American women with breast cancer have
higher fatality rates and a later stage at diagnosis.
D. A family history of breast cancer, especially in
first-degree relatives, increases the risk.
E. A history of breast cancer increases a woman's
risk for subsequent breast cancers. If the woman
has no family history of breast cancer, then the
initial occurrence was sporadic, and the incidence
for developing a second breast cancer is 1% per
year. If the initial occurrence was hereditary, the
incidence for developing a second breast cancer
is 3% per year. Approximately 10% of women with
breast cancer will develop a second primary
breast cancer.
F. Familial or Genetic Risk Factors. A mutation in
a tumor-suppresser gene occurs in 1 of 400
women and is located on chromosome 17q. Carri-
ers of a BRCA1 mutation have an 85% lifetime
risk of developing breast cancer. In addition, the
risk of colon and ovarian cancers is also in-
creased (40% to 50%) in these groups. The 70%
of breast cancer patients who do not have inher-
ited mutations on BRCA1 have mutations on
BRCA2. The cumulative lifetime risk of breast
cancer in a woman with the BRCA2 mutation is
87%.
G. Conclusions. Seventy-five% of women with
newly diagnosed breast cancer demonstrate no
specific, identifiable risk factor. Most
premenopausal breast cancer cases are geneti-
cally determined. In contrast, many post-meno-
pausal cases are environmentally related.
II. Screening Guidelines
A. Breast Self-Examination. All women older than
age 20 years should perform regular monthly
breast self-examinations. Menstruating women
should examine their breasts in the first 7 to 10
days of the menstrual cycle.

Breast Screening Criteria

Age Clinical Mammogra-

Breast Exam- phy
ination

30-39 Every 1-3 years None

40-49 Annual Optional 1-2

years

> 50 Annual Annual

Women aged 50 to 69 years should be offered mammogra-

phy and receive a clinical breast examination every 1 to 2
years.

B. Clinical Breast Examination (CBE) is recom-

mended every 1 to 3 years for women aged 30 to
39 years and annually for those aged 40 years
and older.
 C. Mammography alone is 75% sensitive, and,
when combined with CBE, the screening sensitiv-
ity for detecting breast cancer increases to 88%.
Screening guidelines from the US Preventive
Services Task Force suggest mammography
alone or with CBE every 1 to 2 years for women
aged 50 to 69 years. Recent evidence suggests a
benefit from annual mammography with or without
CBE for women aged 40 to 49 years.
III. History and physical examination
A. In the woman with a suspicious breast mass, risk
factors and a family history of breast cancers
should be assessed. A personal history of radia-
tion to the chest or breast, breast masses, biop-
sies, history of collagen vascular disease, and
menstrual and gynecologic history are also impor-
tant. Symptoms of nipple discharge, pain, skin
changes, or rashes may occur.
B. On physical examination, the breast mass should
be palpated for size, position, adherence of the
tumor to the skin or chest wall, density,
fluctuance, and tenderness. In addition, both
breasts and axillae should be examined for other
tumors and any lymph nodes. A search for
supraclavicular lymph nodes should also be con-
ducted.
C. Any evidence of skin changes, ulceration, peau
d'orange (thickening of skin to resemble an or-
ange skin), or lymphedema is suspicious for lo-
cally advanced cancer.
D. Immediate mammography should be obtained. A
white blood count, hematocrit, and erythrocyte
sedimentation rate may be needed if cancer is
found.
IV. Diagnosis
A. The definitive diagnosis is made by pathological
evaluation of tissue.
B. A combination of clinical breast examination,
mammography, and fine-needle aspiration and
biopsy may be sufficient to make a diagnosis. If all
studies are "benign," there is a >99% chance that
a benign breast lesion is present.
C. Open biopsy in the operating room or wire-local-
ization of a suspicious lesion noted on mammog-
raphy may be necessary if fine-needle aspiration
and biopsy is nondiagnostic. Biopsy by stereo-
tactic technique in radiology also may be used to
obtain tissue for diagnosis of the suspicious area.
V. Definition and classification of breast cancer for
staging
A. The definition for staging and the classification of
stages for breast cancer follow the system of the
International Union Against Cancer. This system
is based on the tumor, nodes, and metastases
(TNM) nomenclature.

Definitions for Breast Cancer Staging

Tumor

TIS Carcinoma in situ (intraductal carcinoma,

Iobular)

T0 No evidence of primary tumor

T1 Tumor <2 cm in greatest dimension

T2 Tumor >2 cm but <5 cm in greatest dimension

T3 Tumor >5 cm in greatest dimension

T4 Tumor of any size with direct extension into

chest wall or skin

Nodes

N0 No regional lymph node metastases

N1 Metastases to movable ipsilateral axillary

node(s)

N2 Metastases to ipsilateral axillary lymph node(s),

fixed to one another or other structures

Metastases

M0 No distant metastases

MI Metastases to movable ipsilateral axillary

node(s);
metastases to ipsilateral axillary lymph node(s);
fixed
to one another or other structures; or
metastases to
ipsilateral internal mammary lymph node(s);
distant
metastases

Classification of Breast Cancer Staging

Stage Description*

0 TIS, N0, M0

I TI, N0, M0

IIA T0, NI, M0

IIB T2, NI, M0, or T3, N0, M0

IIIA T0, N2, M0, or TI, N2, M0, or T2, N2, M0, or
T3, NI, or N2, M0

IIIB T4, any N, M0 or any T, N3

IV Any T, any N, MI

*Tumor/nodes/metastases

B. The HER-2 gene (c-erbB-2, HER-2/neu) has

been identified, and the HER-2 receptor is corre-
lated with aggressive biological behavior of the
cancer and a poor clinical outcome.
C. The staging of breast cancer dictates not only the
prognosis but also directs treatment modality
recommendations. The prognosis for women is
based on their age, tumor type, initial tumor size,
presence of nodes and staging, and hormone-re-
ceptor status. The overall 10-year survival rates
for the more common breast cancer stages are
>90% for stage 0, >75% for stage I, >50% for
stage IIA, and approximately 50% for stage IIB.
VI. Treatment of breast cancer
A. Treatment choices for ductal carcinoma in situ, a
stage 0 cancer, include 1) mastectomy, 2)
lumpectomy followed by radiation therapy, or 3)
lumpectomy followed by radiation therapy and
then tamoxifen if the tumor is estrogen-receptor
test positive.
B. Surgical Treatment
1. Conservative therapy and radiation result in at
least as good a prognosis as radical mastec-
tomy. Skin-sparing mastectomy involves re-
moving all the breast tissue, the nipple, and
the areolar complex. Reconstruction is then
completed with a natural-appearing breast.
This procedure is considered for those women
with ductal carcinoma in situ or T1 or T2 inva-
sive carcinomas. The recurrence rate for this
procedure is comparable with a modified radi-
cal mastectomy.
2. Local excision of the tumor mass
(lumpectomy) followed by lymph node staging
and subsequent adjuvant hormone therapy,
chemotherapy, or radiation therapy is an ac-
cepted treatment. Long-term studies have
found that recurrence rates are similar when
lumpectomy was compared with radiation ther-
apy and mastectomy.
C. Radiation Therapy. External beam radiation
therapy has proven effective in preventing recur-
rence of breast cancer and for palliation of pain.
The risk of relapse after radiation therapy ranges
from 4% to 10%. Lumpectomy can now be per-
formed followed by implantation of high-dose
brachytherapy catheters.
D. Anti-Hormonal Therapy. Hormonal therapy is
indicated for those tumors that test positive for
hormone receptors. Tamoxifen has both estro-
genic and anti-estrogenic effects. In women who
are older than 50 years with breast cancers that
test positive for hormone receptors, tamoxifen
use produces a 20% increase in 5-year survival
rates. The response rate in advanced cases in-
creases to 35%.
E. Chemotherapy
1. Chemotherapy is used in women at risk for
metastatic disease. Cytotoxic agents used
include methotrexate, fluorouracil,
cyclophosphamide (Cytoxan, Neosar),
doxorubicin, mitoxantrone (Novantrone), and
paclitaxel (Taxol). In the management of stage
0 disease, chemotherapy is not used initially.
2. Stage I and stage II disease are treated with
chemotherapy based on the relative risk of
systemic recurrence. This risk is often based
on the woman's age, axillary lymph node in-
volvement, tumor size, hormone receptor sta-
tus, histologic tumor grade, and cellular
aggressiveness. Systemic chemotherapy is
recommended for women with stage I disease
who have node-negative cancers and a tumor
size >1 cm in diameter.
3. Women with stage IIA breast cancer are
treated with adjuvant chemotherapy with or
without tamoxifen. Some women with positive
lymph nodes are placed on chemotherapy,
including doxorubicin, fluorouracil, and
methotrexate.
4. In women with stage III breast cancer, similar
agents are selected. Doxorubicin is particu-
larly useful in treating inflammatory breast
cancer. In women with stage IIIB cancer, che-
motherapy is usually administered before pri-
mary surgery or radiation therapy.
References: See page 208.

Obstetrics
Prenatal Care
Prenatal care should make an early, accurate estimation
of gestational age, identify patients at risk for complica-
tions, and monitor the health status of both mother and
fetus on an ongoing basis. Patient education and com-
munication are also important components of prenatal
care.

I. Prenatal history and physical examination.

Women at increased risk of maternal medical compli-
cations, pregnancy complications, or fetal abnormali-
ties should be identified.
A. Diagnosis of pregnancy
1. Amenorrhea is usually the first sign of concep-
tion. Other symptoms include breast fullness
and tenderness, skin changes, nausea, vomit-
ing, urinary frequency, and fatigue.
2. Pregnancy tests. Urine pregnancy tests may
be positive within days of the first missed men-
strual period. Serum beta human chorionic
gonadotropin (HCG) is accurate up to a few
days after implantation.
3. Fetal movements ("quickening") are first felt
by the patient at 17-19 weeks.
4. Ultrasound will visualize a gestational sac at
5-6 weeks and a fetal pole with movement and
cardiac activity by 7-8 weeks. Ultrasound can
estimate fetal age accurately if completed be-
fore 24 weeks.
5. Estimated date of confinement. The mean
duration of pregnancy is 40 weeks from the
LMP. Estimated date of confinement (EDC) can
be calculated by Nägele's rule: Add 7 days to
the first day of the LMP, then subtract 3
months.
B. Contraceptive history. Recent oral contraceptive
usage often causes postpill amenorrhea, and may
cause erroneous pregnancy dating.
C. Gynecologic and obstetric history
1. Gravidity is the total number of pregnancies.
Parity is expressed as the number of term
pregnancies, preterm pregnancies, abortions,
and live births.
2. The character and length of previous labors,
type of delivery, complications, infant status,
and birth weight are recorded.
3. Assess prior cesarean sections and determine
type of C-section (low transverse or classical),
and determine reason it was performed.
D. Medical and surgical history and prior hospital-
izations are documented.
E. Medications and allergies are recorded.
F. Family history of medical illnesses, hereditary
illness, or multiple gestation is sought.
G. Social history. Cigarettes, alcohol, or illicit drug
use.
H. Review of systems. Abdominal pain, constipa-
tion, headaches, vaginal bleeding, dysuria or uri-
nary frequency, or hemorrhoids.

Basic Prenatal Medical History

 Endocrine disorder Autoimmune disorder
Thyroid Systemic lupus
Adrenal erythematosus
Diabetes Rheumatoid arthritis

Cardiovascular disease History of blood transfusion

Hypertension Pulmonary disease
Arrhythmia Asthma
Congenital anomalies Tuberculosis
Rheumatic Fever
Thromboembolic dis-
ease

Kidney disease Breast disorders

Pyelonephritis Infectious diseases
Urinary tract infections Herpes
Anomalies Gonorrhea
Chlamydia
Syphilis
HIV

Neurologic or muscular dis- Gynecologic history

orders Abnormal PAP smear
Seizure disorder Genital tract disease or
Aneurysm procedures
Arteriovenous malfor-
mation

Gastrointestinal disease Surgical procedures

Hepatitis Allergies
Gall bladder disease Medications
Inflammatory bowel Substance abuse
disease Alcohol
Cigarettes
Illicit drugs

Current Pregnancy History

Medications taken Vaginal bleeding

Alcohol use Nausea, vomiting, weight
Cigarette use loss
Infections
Illicit drug use Exposure to toxic sub-
Exposure to radiation stances

Initial Prenatal Assessment of past Obstetrical

History

Date of delivery Type of anesthesia

Gestational age at delivery
Location of delivery
Sex of child
Birth weight
Mode of delivery
Length of labor
Outcome (miscarriage, still-
birth, ectopic, etc.)
Details (eg, type of cesar-
ean section scar, forceps,
etc.)
Complications (maternal,
fetal child)

I. Physical examination
1. Baseline blood pressure, weight, and height
should be recorded as part of the examination.
Funduscopic examination, thyroid, breast,
lungs, and heart are examined.
2. An extremity and neurologic exam are com-
pleted, and the presence of a cesarean section
scar is sought.
3. Fetal heart tones can be detected as early as
9-12 weeks from the last menstrual period
(LMP) by Doppler. The normal fetal heart rate
is 120-160 beats per minute. Transvaginal ul-
trasound can visualize fetal cardiac motion as
early as 5.5 to 6.0 weeks.
4. Pelvic examination
a. Pap smear, culture for gonorrhea, and
Chlamydia testing are completed routinely.
Adnexa are palpated for masses.
b. Estimation of gestational age by uterine
size
(1) The nongravid uterus is 3 x 4 x 7 cm.
The uterus begins to change in size at 5-
6 weeks.
(2) Gestational age is estimated by uterine
size: 8 weeks = 2 x normal size; 10
weeks = 3 x normal; 12 weeks = 4 x nor-
mal.
(3) At 12 weeks the fundus becomes palpa-
ble at the symphysis pubis.
(4) At 16 weeks, the uterus is midway be-
tween the symphysis pubis and the um-
bilicus.
(5) At 20 weeks, the uterus is at the umbili-
cus. After 20 weeks, there is a correla-
tion between the number of weeks of
gestation and the number of centimeters
from the pubic symphysis to the top of
the fundus.
(6) Uterine size that exceeds the gestational
dating by 3 or more weeks suggests mul-
tiple gestation, molar pregnancy, or
(most commonly) an inaccurate date for
LMP. Ultrasonography will confirm inac-
curate dating or intrauterine growth fail-
ure.
II. Initial visit laboratory testing
A. Routine. A standard panel of laboratory tests
should be obtained on every pregnant woman at
the first prenatal visit. Chlamydia screening is
recommended for all pregnant women.

Initial Prenatal Laboratory Examination

Blood type and antibody Urinary infection screen

screen Hepatitis B surface antigen
Rhesus type HIV counseling and testing
Hematocrit or hemoglobin Chlamydia
TSH, free T4 Gonorrhea
PAP smear
Rubella status (immune or
nonimmune)
Syphilis screen

B. Human immunodeficiency virus

1. HIV testing is recommended for all pregnant
women.
2. Retesting in the third trimester (around 36
weeks of gestation) is recommended for
women at high risk for acquiring HIV infection.
C. At-risk women should receive additional
tests:
1. Gonorrhea, tuberculosis and red cell indices to
screen for thalassemia (eg, MCV <80), hemo-
globin electrophoresis to detect hemoglobin-
opathies (eg, sickle cell, thalassemias)
2. Hexosaminidase A for Tay Sachs screening
(serum test in nonpregnant and leukocyte
assay in pregnant individuals), DNA analysis
for Canavan's disease, cystic fibrosis carrier
testing, serum phenylalanine level,
toxoplasmosis screen, and Hepatitis C anti-
bodies.
3. Testing for sexually transmitted diseases
(eg, HIV, syphilis, hepatitis B surface antigen,
chlamydia, gonorrhea) should be repeated in
the third trimester in any woman at high risk
for acquiring these infections; all women under
age 25 years should be retested for
Chlamydia trachomatis late in pregnancy.
D. CBC, AB blood typing and Rh factor, antibody
screen, rubella, VDRL/RPR, hepatitis B sur-
face Ag.
E. Pap smear, urine pregnancy test, urinalysis.
Cervical culture for gonorrhea and chlamydia.
F. Tuberculosis skin testing, HIV counsel-
ing/testing.
G. Hemoglobin electrophoresis is indicated in risks
groups, such as sickle hemoglobin in African
patients, B-thalassemia in Mediterranean pa-
tients, and alpha-thalassemia in Asian patients.
Tay-Sachs carrier testing is indicated in Jewish
patients.
III. Initial patient education
A. Frequency of prenatal visits, recommendations
for nutrition, weight gain, exercise, rest, and sex-
ual activity, routine pregnancy monitoring (eg,
weight, urine dipstick, blood pressure, uterine
growth, fetal activity and heart rate), listeria pre-
cautions, toxoplasmosis precautions (eg, hand
washing, eating habits, cat care) should be dis-
cussed. Pregnant women should continue wear-
ing three-point seat belts during pregnancy. The
lap belt is placed across the hips and below the
uterus; the shoulder belt goes between the
breasts and lateral to the uterus.
B. Abstinence from alcohol, cigarettes, illicit drugs
should be assessed. Information on the safety of
commonly used nonprescription drugs, signs and
symptoms to be reported should be discussed,
as appropriate for gestational age (eg, vaginal
bleeding, ruptured membranes, contractions,
decreased fetal activity).
C. Headache and backache. Acetaminophen
(Tylenol) 325-650 mg every 3-4 hours is effec-
tive. Aspirin is contraindicated.
D. Nausea and vomiting. First-trimester morning
sickness may be relieved by eating frequent,
small meals, getting out of bed slowly after eating
a few crackers, and by avoiding spicy or greasy
foods. Promethazine (Phenergan) 12.5-50 mg
PO q4-6h prn or diphenhydramine (Benadryl) 25-
50 mg tid-qid is useful.
E. Constipation. A high-fiber diet with psyllium
(Metamucil), increased fluid intake, and regular
exercise should be advised. Docusate (Colace)
100 mg bid may provide relief.
IV. Nutrition, vitamins, and weight gain
A. All pregnant women should be encouraged to eat
a well-balanced diet. Folic acid is recommended
in the preconceptional and early prenatal period
to prevent neural tube defects (NTDs). A stan-
dard prenatal multivitamin satisfies the require-
ments of most pregnant women.
B. Nutritional recommendations for pregnant
women are based upon the prepregnancy body
mass index (BMI). A weight gain of 12.5 to 18 kg
(28 to 40 lb) for underweight women (BMI<19.8),
7 to 11.5 kg (15 to 25 lb) for overweight women
(BMI $26), and 11.5 to 16 kg (25 to 35 lb) for
women of average weight (BMI 19.8 to 26.0) is
recommended.
V. Clinical assessment at first trimester prenatal
visits
A. Routine examination at each subsequent visit
consists of measurement of blood pressure and
weight, measurement of the uterine fundus to
assess fetal growth, auscultation of fetal heart
tones, and determination of fetal presentation
and activity. The urine is typically screened for
protein and glucose at each visit.
B. At 9 to 12 weeks the fetal heart usually can be
heard by of gestation using a Doppler instrument.
Transvaginal ultrasound can determine fetal via-
bility as early as 5.5 to 6.5 weeks.
C. Aneuploidy testing with full integrated test.
The full integrated test consists of ultrasound
measurement of nuchal translucency thickness
combined with a pregnancy-associated plasma
protein-A at 10 to 13 weeks.

Frequency of Prenatal Care Visits in Low-Risk

Pregnancies

<28 weeks Every month

28-36 weeks Every 2 weeks

36-delivery Every 1 week until deliv-

ery

VI. Clinical assessment at second trimester visits

A. Questions for each follow-up visit
1. First detection of fetal movement (quicken-
ing) should occur at around 17 weeks in a
multigravida and at 19 weeks in a
primigravida. Fetal movement should be doc-
umented at each visit after 17 weeks.
2. Vaginal bleeding or symptoms of preterm
labor should be sought.
B. Fetal heart rate is documented at each visit.
VII. Second-trimester laboratory
A. Maternal serum testing at 15-18 weeks: Qua-
druple markers should be obtained at 15 to 18
weeks, measuring alpha-fetoprotein (AFP),
unconjugated estriol (uE3), hCG, and inhibin A.
Genetic amniocentesis should be offered to
patients who screen positive, and it should be
offered if a birth defect has occurred in the
mother, father, or in previous offspring.
B. Screening ultrasound. Ultrasound measure-
ment of crown-rump length at 7 to 14 weeks is
the most accurate technique for estimation of
gestational age; it is accurate within three to five
days.
C. At 24-28 weeks, a one-hour Glucola (blood glu-
cose measurement 1 hour after 50-gm oral glu-
cose) is obtained to screen for gestational diabe-
tes. Those with a particular risk (eg, previous
gestational diabetes or fetal macrosomia), re-
quire earlier testing. If the 1 hour test result is
>140 mg/dL, a 3-hour glucose tolerance test is
necessary.
D. Second trimester education. Discomforts in-
clude backache, round ligament pain, constipa-
tion, and indigestion.
VIII. Clinical assessment at third trimester visits
A. Fetal movement is documented. Vaginal bleed-
ing or symptoms of preterm labor should be
sought. Preeclampsia symptoms (blurred vision,
 headache, rapid weight gain, edema) are sought.

B. Fetal heart rate is documented at each visit.

C. At 26-30 weeks, repeat hemoglobin and
hematocrit are obtained to determine the need
for iron supplementation.
D. At 28-30 weeks, an antibody screen is obtained
in Rh-negative women, and D immune globulin
(RhoGAM) is administered if negative.
E. At 36 weeks, repeat serologic testing for syphilis
is recommended for high risk groups.
F. Sexually transmitted disease. Testing for sexu-
ally transmitted diseases (eg, HIV, syphilis, hepa-
titis B surface antigen, chlamydia, gonorrhea)
should be repeated in the third trimester in any
woman at high risk for acquiring these infections;
all women under age 25 years should be retested
for Chlamydia trachomatis late in pregnancy.
G. Screening for group B streptococcus coloni-
zation at 35-37 weeks. All pregnant women
should be screened for group B beta-hemolytic
streptococcus (GBS) colonization with swabs of
both the lower vagina and rectum at 35 to 37
weeks of gestation. The only patients who are
excluded from screening are those with GBS
bacteriuria earlier in the current pregnancy or
those who gave birth to a previous infant with
invasive GBS disease. These latter patients are
not included in the screening recommendation
because they should receive intrapartum antibi-
otic prophylaxis regardless of the colonization
status.
H. Influenza immunization is recommended for
women in the second and third trimesters and for
high-risk women prior to influenza season re-
gardless of stage of pregnancy.
I. Third trimester education
1. Signs of labor. The patient should call physi-
cian when rupture of membranes or contrac-
tions have occurred every 5 minutes for one
hour.
2. Danger signs. Preterm labor, rupture of mem-
branes, bleeding, edema, signs of preeclamp-
sia.
3. Common discomforts. Cramps, edema, fre-
quent urination.
J. At 36 weeks, a cervical exam may be com-
pleted. Fetal position should be assessed by
palpation (Leopold’s Maneuvers).
References: See page 208.

Normal Labor
Labor consists of the process by which uterine contrac-
tions expel the fetus. A term pregnancy is 37 to 42
weeks from the last menstrual period (LMP).
I. Obstetrical History and Physical Examination
A. History of the present labor
1. Contractions. The frequency, duration, onset,
and intensity of uterine contractions should be
determined. Contractions may be accompanied
by a '’bloody show" (passage of blood-tinged
mucus from the dilating cervical os). Braxton
Hicks contractions are often felt by patients
during the last weeks of pregnancy. They are
usually irregular, mild, and do not cause cervi-
cal change.
2. Rupture of membranes. Leakage of fluid may
occur alone or in conjunction with uterine con-
tractions. The patient may report a large gush of
fluid or increased moisture. The color of the
liquid should be determine, including the pres-
ence of blood or meconium.
3. Vaginal bleeding should be assessed. Spotting
or blood-tinged mucus is common in normal
labor. Heavy vaginal bleeding may be a sign of
placental abruption.
4. Fetal movement. A progressive decrease in
fetal movement from baseline, should prompt
an assessment of fetal well-being with a
nonstress test or biophysical profile.
B. History of present pregnancy
1. Estimated date of confinement (EDC) is cal-
culated as 40 weeks from the first day of the
LMP.
2. Fetal heart tones are first heard with a Doppler
instrument 10-12 weeks from the LMP.
3. Quickening (maternal perception of fetal move-
ment) occurs at about 17 weeks.
4. Uterine size before 16 weeks is an accurate
measure of dates.
5. Ultrasound measurement of fetal size before
24 weeks of gestation is an accurate measure
of dates.
6. Prenatal history. Medical problems during this
pregnancy should be reviewed, including uri-
nary tract infections, diabetes, or hypertension.
7. Antepartum testing. Nonstress tests, contrac-
tion stress tests, biophysical profiles.
8. Review of systems. Severe headaches,
scotomas, hand and facial edema, or epigastric
pain (preeclampsia) should be sought. Dysuria,
urinary frequency or flank pain may indicate
cystitis or pyelonephritis.
C. Obstetrical history. Past pregnancies, durations
and outcomes, preterm deliveries, operative deliv-
eries, prolonged labors, pregnancy-induced hyper-
tension should be assessed.
D. Past medical history of asthma, hypertension, or
renal disease should be sought.
II. Physical examination
A. Vital signs are assessed.
B. Head. Funduscopy should seek hemorrhages or
exudates, which may suggest diabetes or hyper-
tension. Facial, hand and ankle edema suggest
preeclampsia.
C. Chest. Auscultation of the lungs for wheezes and
crackles may indicate asthma or heart failure.
D. Uterine Size. Until the middle of the third trimes-
ter, the distance in centimeters from the pubic
symphysis to the uterine fundus should correlate
with the gestational age in weeks. Toward term,
the measurement becomes progressively less
reliable because of engagement of the presenting
part.
E. Estimation of fetal weight is completed by palpa-
tion of the gravid uterus.
F. Leopold's maneuvers are used to determine the
position of the fetus.
1. The first maneuver determines which fetal
pole occupies the uterine fundus. The breech
moves with the fetal body. The vertex is rounder
and harder, feels more globular than the
breech, and can be moved separately from the
fetal body.
2. Second maneuver. The lateral aspects of the
uterus are palpated to determine on which side
the fetal back or fetal extremities (the small
parts) are located.
3. Third maneuver. The presenting part is moved
from side to side. If movement is difficult, en-
gagement of the presenting part has occurred.
4. Fourth maneuver. With the fetus presenting by
vertex, the cephalic prominence may be palpa-
ble on the side of the fetal small parts.
G. Pelvic examination. The adequacy of the bony
pelvis, the integrity of the fetal membranes, the
degree of cervical dilatation and effacement, and
the station of the presenting part should be deter-
mined.
H. Extremities. Severe lower extremity or hand
edema suggests preeclampsia. Deep-tendon
hyperreflexia and clonus may signal impending
seizures.
I. Laboratory tests
1. Prenatal labs should be documented, including
CBC, blood type, Rh, antibody screen, serologic
test for syphilis, rubella antibody titer, urinalysis,
culture, Pap smear, cervical cultures for gonor-
rhea and Chlamydia, and hepatitis B surface
antigen (HbsAg).
2. During labor, the CBC, urinalysis and RPR are
repeated. The HBSAG is repeated for high-risk
patients. A clot of blood is placed on hold.
J. Fetal heart rate. The baseline heart rate, variabil-
ity, accelerations, and decelerations are recorded.
III. Normal labor
A. Labor is characterized by uterine contractions of
sufficient frequency, intensity, and duration to re-
sult in effacement and dilatation of the cervix.
B. The first stage of labor starts with the onset of
regular contractions and ends with complete di-
latation (10 cm). This stage is further subdivided
into the latent and an active phases.
1. The latent phase starts with the onset of regular
uterine contractions and is characterized by
slow cervical dilatation to 4 cm. The latent
phase is variable in length.
2. The active phase follows and is characterized
by more rapid dilatation to 10 cm. During the
active phase of labor, the average rate of cervi-
cal dilatation is 1.5 cm/hour in the multipara and
1.2 cm/hour in the nullipara.
C. The second stage of labor begins with complete
dilatation of the cervix and ends with delivery of the
infant. It is characterized by voluntary and involun-
tary pushing. The average second stage of labor is
one-half hour in a multipara and 1 hour in the
primipara.
D. The third stage of labor begins with the delivery
of the infant and ends with the delivery of the pla-
centa.
E. Intravenous fluids. IV fluid during labor is usually
Ringer's lactate or 0.45% normal saline with 5%
dextrose. Intravenous fluid infused rapidly or given
as a bolus should be dextrose-free because ma-
ternal hyperglycemia can occur.
F. Activity. Patients in the latent phase of labor are
usually allowed to walk.
G. Narcotic and analgesic drugs
1. Nalbuphine (Nubain) 5 to 10 mg SC or IV q2-
3h.
2. Butorphanol (Stadol) 2 mg IM q3-4h or 0.5-1.0
mg IV q1.5-2.0h OR
3. Meperidine (Demerol) 50 to 100 mg IM q3-4h or
10 to 25 mg IV q1.5-3.0 h OR
4. Narcotics should be avoided if their peak action
will not have diminished by the time of delivery.
Respiratory depression is reversed with
naloxone (Narcan): Adults, 0.4 mg IV or IM and
neonates, 0.01 mg/kg.

Labor History and Physical

Chief compliant: Contractions, rupture of mem-
branes.
HPI: ___ year old Gravida (number of pregnancies)
Para (number of deliveries).
Gestational age, last menstrual period, estimated
date of confinement.
Contractions (onset, frequency, intensity), rupture of
membranes (time, color). Vaginal bleeding (consis-
tency, quantity, bloody show); fetal movement.
Fetal Heart Rate Strip: Baseline rate, accelerations,
reactivity, decelerations, contraction frequency.
Dates: First day of last menstrual period, estimated
date of confinement. Ultrasound dating.
Prenatal Care: Date of first exam, number of visits;
has size been equal to dates? infections, hyperten-
sion, diabetes.
Obstetrical History: Dates of prior pregnancies,
gestational age, route (C-section with indications
and type of uterine incision), weight, complications,
length of labor, hypertension.
Gynecologic History: Menstrual history (menarche,
interval, duration), herpes, gonorrhea, chlamydia,
abortions; oral contraceptives.
Past Medical History: Illnesses, asthma, hyperten-
sion, diabetes, renal disease, surgeries.
Medications: Iron, prenatal vitamins.
Allergies: Penicillin, codeine?
Social History: Smoking, alcohol, drug use.
Family History: Hypertension, diabetes, bleeding
disorders.
Review of Systems: Severe headaches, scotomas,
blurred vision, hand and face edema, epigastric
pain, pruritus, dysuria, fever.

Physical Exam
General Appearance:
Vitals: BP, pulse, respirations, temperature.
HEENT: Funduscopy, facial edema, jugular venous
distention.
Chest: Wheezes, rhonchi.
Cardiovascular: Rhythm, S1, S2, murmurs.
Abdomen: Fundal height, Leopold's maneuvers (lie,
presentation). Estimated fetal weight (EFW), tender-
ness, scars.
Cervix: Dilatation, effacement, station, position,
status of membranes, presentation. Vulvar herpes
lesions.
Extremities: Cyanosis, clubbing, edema.
Neurologic: Deep tender reflexes, clonus.
Prenatal Labs: Obtain results of one hour post
glucola, RPR/VDRL, rubella, blood type, Rh, CBC,
Pap, PPD, hepatitis BsAg, UA, C and S.
Current Labs: Hemoglobin, hematocrit, glucose,
UA; urine dipstick for protein.
Assessment: Intrauterine pregnancy (IUP) at 40
weeks, admitted with the following problems:
Plan: Anticipated type of labor and delivery. List plan
for each problem.
 H. Epidural anesthesia
1. Contraindications include infection in the lum-
bar area, clotting defect, active neurologic dis-
ease, sensitivity to the anesthetic, hypovolemia,
and septicemia.
2. Risks include hypotension, respiratory arrest,
toxic drug reaction, and rare neurologic compli-
cations. An epidural has no significant effect on
the progress of labor.
3. Before the epidural is initiated, the patient is
hydrated with 500-1000 mL of dextrose-free
intravenous fluid.

Labor and Delivery Admitting

Orders
Admit: Labor and Delivery
Diagnoses: Intrauterine pregnancy at ____ weeks.
Condition: Satisfactory
Vitals: q1 hr per routine
Activity: May ambulate as tolerated.
Nursing: I and O. Catheterize prn; external or inter-
nal monitors.
Diet: NPO except ice chips.
IV Fluids: Lactated Ringers with 5% dextrose at 125
cc/h.
Medications:
Epidural at 4-5 cm.
Oxytocin (Pitocin) 6 mU per minute IV, increase
dose by 6 mU per minute every 15 minutes until con-
tractions occur every 3 minutes.
Nalbuphine (Nubain) 5-10 mg IV/SC q2-3h prn OR
Butorphanol (Stadol) 0.5-1 mg IV q1.5-2h prn OR
Meperidine (Demerol) 25-75 mg slow IV q1.5-3h prn
pain AND
Promethazine (Phenergan) 25-50 mg, IV q3-4h prn
nausea OR
Hydroxyzine (Vistaril) 25-50 mg IV q3-4h prn
Fleet enema PR prn constipation.
Labs: CBC, dipstick urine protein, blood type and Rh,
antibody screen, VDRL, HBsAg, rubella, type and screen
(C-section).

I. Intrapartum antibiotic prophylaxis for group B

streptococcus is recommended for the following:
1. Pregnant women with a positive screening culture
unless a planned Cesarean section is performed in
the absence of labor or rupture of membranes
2. Pregnant women who gave birth to a previous infant
with invasive GBS disease
3. Pregnant women with documented GBS bacteriuria
during the current pregnancy
4. Pregnant women whose culture status is unknown
(culture not performed or result not available) and
who also have delivery at <37 weeks of gestation,
amniotic membrane rupture for >18 hours, or
intrapartum temperature >100.4ºF (>38ºC)
5. The recommended IAP regimen is penicillin G (5
million units IV initial dose, then 2.5 million units IV
Q4h). In women with non-immediate-type penicillin-
allergy, cefazolin (Ancef, 2 g initial dose, then 1 g
Q8h) is recommended. Clindamycin (900 mg IV
Q8h) or erythromycin (500 mg IV Q6h) are recom-
mended for patients at high risk for anaphylaxis to
penicillins as long as their GBS isolate is docu-
mented to be susceptible to both clindamycin and
erythromycin.
IV. Normal spontaneous vaginal delivery
A. Preparation. As the multiparous patient approaches
complete dilatation or as the nulliparous patient begins
to crown the fetal scalp, preparations are made for
delivery.
B. Maternal position. The mother is usually placed in the
dorsal lithotomy position with left lateral tilt.
C. Delivery of a fetus in an occiput anterior position
1. Delivery of the head
a. The fetal head is delivered by extension as the
flexed head passes through the vaginal introitus.
b. Once the fetal head has been delivered, external
rotation to the occiput transverse position occurs.
c. The oropharynx and nose of the fetus are
suctioned with the bulb syringe. A finger is
passed into the vagina along the fetal neck to
check for a nuchal cord. If one is present, it is
lifted over the vertex. If this cannot be accom-
plished, the cord is doubly clamped and divided.
d. If shoulder dystocia is anticipated, the shoulders
should be delivered immediately.
2. Episiotomy consists of incision of the perineum,
enlarging the vaginal orifice at the time of delivery. If
indicated, an episiotomy should be performed when
3-4 cm of fetal scalp is visible.
a. With adequate local or spinal anesthetic in place,
a medial episiotomy is completed by incising the
perineum toward the anus and into the vagina.
b. Avoid cutting into the anal sphincter or the rec-
tum. A short perineum may require a
mediolateral episiotomy.
c. Application of pressure at the perineal apex with
a towel-covered hand helps to prevent extension
of the episiotomy.
3. Delivery of the anterior shoulder is accomplished
by gentle downward traction on the fetal head. The
posterior shoulder is delivered by upward traction.
4. Delivery of the body. The infant is grasped around
the back with the left hand, and the right hand is
placed, near the vagina, under the baby's buttocks,
supporting the infant’s body. The infant’s body is
rotated toward the operator and supported by the
operator’s forearm, freeing the right hand to suction
the mouth and nose. The baby's head should be
kept lower than the body to facilitate drainage of
secretions.
5. Suctioning of the nose and oropharynx is repeated.
6. The umbilical cord is doubly clamped and cut,
leaving 2-3 cm of cord.
D. Delivery of the placenta
1. The placenta usually separates spontaneously from
the uterine wall within 5 minutes of delivery. Gentle
fundal massage and gentle traction on the cord
facilitates delivery of the placenta.
2. The placenta should be examined for missing coty-
ledons or blind vessels. The cut end of the cord
should be examined for 2 arteries and a vein. The
absence of one umbilical artery suggests a congeni-
tal anomaly.
3. Prophylaxis against excessive postpartum blood
loss consists of external fundal massage and
oxytocin (Pitocin), 20 units in 1000 mL of IV fluid at
100 drops/minute after delivery of the placenta.
Oxytocin can cause marked hypotension if adminis-
tered as a IV bolus.
4. After delivery of the placenta, the birth canal is in-
spected for lacerations.

Delivery Note
1. Note the age, gravida, para, and gestational age.
2. Time of birth, type of birth (spontaneous vaginal delivery),
position (left occiput anterior).
3. Bulb suctioned, sex, weight, APGAR scores, nuchal cord, and
number of cord vessels.
4. Placenta expressed spontaneously intact. Describe episiotomy
degree and repair technique.
5. Note lacerations of cervix, vagina, rectum, perineum.
6. Estimated blood loss:
7. Disposition: Mother to recovery room in stable condition. Infant
to nursery in stable condition.

Routine Postpartum Orders

Transfer: To recovery room, then postpartum ward when stable.
Vitals: Check vitals, bleeding, fundus q15min x 1 hr or until stable,
then q4h.
Activity: Ambulate in 2 hours if stable
Nursing Orders: If unable to void, straight catheterize; sitz baths
prn with 1:1000 Betadine prn, ice pack to perineum prn, record
urine output.
Diet: Regular
IV Fluids: D5LR at 125 cc/h. Discontinue when stable and taking
PO diet.
Medications:
Oxytocin (Pitocin) 20 units in 1 L D5LR at 100 drops/minute or
10 U IM.
FeS04 325 mg PO bid-tid.
Symptomatic Medications:
Acetaminophen/codeine (Tylenol #3) 1-2 tab PO q3-4h prn OR
Oxycodone/acetaminophen (Percocet) 1 tab q6h prn pain.
Milk of magnesia 30 mL PO q6h prn constipation.
Docusate Sodium (Colace) 100 mg PO bid.
Dulcolax suppository PR prn constipation.
A and D cream or Lanolin prn if breast feeding.
Breast binder or tight brazier and ice packs prn if not to breast
feed.
Labs: Hemoglobin/hematocrit in AM. Give rubella vaccine if titer
<1:10.

Active Management of Labor

The active management of labor refers to active control over
the course of labor. There are three essential elements to
active management are careful diagnosis of labor by strict
criteria, constant monitoring of labor, and prompt intervention
(eg, amniotomy, high dose oxytocin) if progress is unsatisfac-
tory.

I. Criteria for active management of labor:

A. Nulliparous
B. Term pregnancy
C. Singleton infant in cephalic presentation
D. No pregnancy complications
E. Experiencing spontaneous onset of labor.
II. Diagnosis of labor
A. The diagnosis of labor is made only when contractions
are accompanied by any one of the following:
1. Bloody show
2. Rupture of the membranes
3. Full cervical effacement
B. Women who meet these criteria are admitted to the
labor unit.
III. Management of labor
A. Rupture of membranes. Intact fetal membranes are
artificially ruptured one hour after the diagnosis of labor
is made to permit assessment of the quantity of fluid
and the presence of meconium. Rupture of the mem-
branes may accelerate labor.
B. Progress during the first stage of labor
1. Satisfactory progress in the first stage of labor is
confirmed by cervical dilatation of at least 1 cm per
hour after the membranes have been ruptured.
2. In the absence of medical contraindications, labor
that fails to progress at the foregoing rate is treated
with oxytocin.
3. Progress during the second stage of labor is
measured by fetal descent and rotation.
a. The second stage of labor is divided into two
phases: the first phase is the time from full dila-
tation until the fetal head reaches the pelvic
floor; the second phase extends from the time
the head reaches the pelvic floor to delivery of
the infant.
b. The first phase of the second stage is character-
ized by descent of the fetal head. If the fetal
head is high in the pelvis at full dilatation, the
woman often has no urge to push and should
not be encouraged to do so. Oxytocin treatment
may be useful if the fetal head fails to descend
after a period of observation.
C. Administration of oxytocin. Oxytocin is administered
for treatment of failure of labor to progress, unless its
use is contraindicated. Oxytocin may only be adminis-
tered if the following conditions are met:
1. Fetal membranes are ruptured
2. Absence of meconium in amniotic fluid
3. Singleton fetus in a vertex position
4. No evidence of fetal distress

High Dose Oxytocin (Pitocin) Regimen

Begin oxytocin 6 mU per minute IV

Increase dose by 6 mU per minute every 15 minutes
Maximum dose: 40 mU per minute

D. Failure to progress (dystocia) is diagnosed when the

cervix fails to dilate at least 1 cm per hour during the
first stage of labor or when the fetal head fails to de-
scend during the second stage of labor. Three possible
causes for failure to progress are possible (excluding
malpresentations and hydrocephalus):
1. Inefficient uterine action
2. Occiput-posterior position
3. Cephalopelvic disproportion.
E. Inefficient uterine action is the most common cause of
dystocia in the nulliparous gravida, especially early in
labor. Secondary arrest of labor after previously satis-
factory progress may be due to an occiput-posterior
position or cephalopelvic disproportion. It is often diffi-
cult for the clinician to differentiate among these enti-
ties, thus oxytocin is administered in all cases of failure
to progress (unless a contraindication exists).
F. In the first stage, progressive cervical dilatation of at
least 1 cm per hour should occur within one hour of
establishing efficient uterine contractions (five to seven
contractions within 15 minutes) with oxytocin. The
second stage is considered prolonged if it extends
longer than two hours in women without epidural anes-
thesia and longer than three hours in women with
epidural anesthesia despite adequate contractions and
oxytocin augmentation.
References: See page 208.
Perineal Lacerations and
Episiotomies
I. First-degree laceration
A. A first degree perineal laceration extends only through
the vaginal and perineal skin.
B. Repair: Place a single layer of interrupted 3-O chromic
or Vicryl sutures about 1 cm apart.
II. Second-degree laceration and repair of midline
episiotomy
A. A second degree laceration extends deeply into the
soft tissues of the perineum, down to, but not includ-
ing, the external anal sphincter capsule. The disruption
involves the bulbocavernosus and transverse perineal
muscles.
B. Repair
1. Proximate the deep tissues of the perineal body by
placing 3-4 interrupted 2-O or 3-O chromic or Vicryl
absorbable sutures. Reapproximate the superficial
layers of the perineal body with a running suture
extending to the bottom of the episiotomy.
2. Identify the apex of the vaginal laceration. Suture
the vaginal mucosa with running, interlocking, 3-O
chromic or Vicryl absorbable suture.
3. Close the perineal skin with a running, subcuticular
suture. Tie off the suture and remove the needle.
III. Third-degree laceration
A. This laceration extends through the perineum and
through the anal sphincter.
B. Repair
1. Identify each severed end of the external anal
sphincter capsule, and grasp each end with an Allis
clamp.
2. Proximate the capsule of the sphincter with 4 inter-
rupted sutures of 2-O or 3-O Vicryl suture, making
sure the sutures do not penetrate the rectal mu-
cosa.
3. Continue the repair as for a second degree lacera-
tion as above. Stool softeners and sitz baths are
prescribed post-partum.
IV. Fourth-degree laceration
A. The laceration extends through the perineum, anal
sphincter, and extends through the rectal mucosa to
expose the lumen of the rectum.
B. Repair
1. Irrigate the laceration with sterile saline solution.
Identify the anatomy, including the apex of the rec-
tal mucosal laceration.
2. Approximate the rectal submucosa with a running
suture using a 3-O chromic on a GI needle extend-
ing to the margin of the anal skin.
3. Place a second layer of running suture to invert the
first suture line, and take some tension from the first
layer closure.
4. Identify and grasp the torn edges of the external
anal sphincter capsule with Allis clamps, and per-
form a repair as for a third-degree laceration. Close
the remaining layers as for a second-degree lacer-
ation.
5. A low-residue diet, stool softeners, and sitz baths
are prescribed post-partum.
References: See page 208.

Antepartum Fetal Heart Rate Assess-

ment
The health of the fetus may be assessed by the fetal heart
rate (FHR). This assessment involves identification of two
types of FHR patterns: those that may be associated with
adverse fetal or neonatal outcomes (ie, nonreassuring pat-
terns) and those that are indicative of fetal well-being (ie,
reassuring patterns). The primary goal is to recognize fetuses
in whom timely intervention will prevent death. A secondary
goal is to avoid fetal neurologic injury.

I. Pathophysiology
A. Effect of gestational age on FHR. Advancing gesta-
tional age is associated with slowing of the baseline
heart rate. At 20 weeks of gestation the average FHR
is 155 beats/min, while at 30 weeks it is 144 beats/min.
B. FHR variability is rarely present before 24 weeks of
gestation, while the absence of variability is abnormal
after 28 weeks of gestation since the parasympathetic
nervous system is developed by the third trimester.
C. Advancing gestational age is also associated with
increased frequency and amplitude of FHR accelera-
tions. Fifty% of normal fetuses demonstrate accelera-
tions with fetal movements at 24 weeks; this proportion
rises to over 95% at 30 weeks of gestation. Before 30
weeks, however, accelerations are typically only 10
beats per minute for 10 seconds rather than the 15
beats per minute sustained for 15 seconds noted after
30 weeks.
D. Nonreactivity of the nonstress test is characterized
by loss of accelerations of the FHR caused by worsen-
ing of hypoxemia.
E. Persistent bradycardia or repetitive late decelera-
tions results from myocardial depression caused by
prolonged and/or severe hypoxemia. Variability is also
lost. Ultimately there is a loss of fetal biophysical activi-
ties, such as breathing, movement, and body tone. At
this stage, the fetus may be acidotic.
II. Fetal heart rate patterns
A. Reassuring patterns. The FHR pattern recorded by
an electronic FHR monitor is typically interpreted as
reassuring or nonreassuring. The presence of a reas-
suring pattern indicates that there is no fetal acidemia
at the time of testing. A reassuring fetal heart rate
pattern has the following components:
1. A baseline fetal heart rate of 110 to 160 bpm
2. Absence of FHR decelerations
3. Age appropriate FHR accelerations
4. Normal FHR variability (6 to 25 bpm)
B. FHR accelerations usually indicate that the fetus is
not acidotic. FHR accelerations and mild variable
decelerations are indicative of a normally functioning
autonomic nervous system.
C. Early decelerations are shallow symmetrical deceler-
ations in which the nadir of the deceleration occurs
simultaneously with the peak of the contraction. Early
decelerations and mild bradycardia (FHR as low as
100 bpm) with normal variability are caused by fetal
head compression and are not associated with fetal
acidosis or poor neonatal outcome.
D. Persistent tachyarrhythmias may cause fetal
hydrops if present for many hours to days. Persistent
bradyarrhythmias are often associated with fetal heart
disease (eg, cardiac conduction defects due to ana-
tomic derangements or autoantibody (SSA, anti-Ro)
induced-cardiomyopathy related to lupus), but seldom
result in hypoxemia or acidosis in fetal life.
E. Nonreassuring FHR patterns are nonspecific and
require further evaluation. The false positive rate for
predicting adverse outcome is high. The fetus may not
be acidotic initially; however, continuation or worsening
of the clinical situation may result in fetal acidosis.
Nonreassuring patterns include:
1. Abnormal variability refers to variability that is
absent (amplitude undetectable), minimal (ampli-
tude 0 to 5 bpm), or marked (amplitude over 25
bpm).
2. Late decelerations are a smooth U-shaped fall in
FHR beginning after the contraction has started,
and ending after the contraction has ended. The
decline in FHR is gradual (>30 seconds from the
onset of the deceleration to its nadir), as is the re-
turn to baseline. The nadir of the deceleration oc-
curs after the peak of the contraction. Mild late
decelerations are a central nervous system re-
sponse to hypoxia, while severe late decelerations
can have a component of myocardial depression.
Late decelerations with absent variability are espe-
cially predictive of fetal acidosis.
3. Sinusoidal heart rate is a pattern of regular vari-
ability resembling a sine wave with a fixed periodic-
ity of three to five cycles per minute and an ampli-
tude of 5 to 40 bpm. Sinusoidal pattern is a re-
sponse to moderate fetal hypoxemia, often caused
by fetal anemia.
4. Variable decelerations are a variable onset of
abrupt slowing of the FHR in association with uter-
ine contractions and are shaped like a U, V, or W.
a. Severe variable decelerations have a late
component, with delayed return to baseline until
after the contraction, during which the fetal pH
falls. They may also display loss of variability or
rebound tachycardia and last longer than 60
seconds or fall to less than 70 bpm.
b. Mild or moderate variable decelerations do
not have a late component, are of short duration
and depth, and end by rapid return to a normal
baseline FHR. They are usually intermittent,
rather than persistent. This pattern is not associ-
ated with acidosis or low Apgar scores .
5. Saltatory pattern refers to excessive variability,
with amplitude >25 bpm and cycles of three to six
times per minute. The pattern is probably related to
mild, compensated fetal hypoxemia and increased
alpha-adrenergic activity.
F. Ominous patterns. Fetal distress is defined as a
pathological condition of the fetus that is likely to cause
fetal or neonatal death or damage if left uncorrected. It
is often associated with fetal acidemia and hypoxemia.
1. There are only a few patterns associated with true
fetal distress; these FHR patterns can be a useful
noninvasive means of assessing for fetal acidemia
and hypoxemia:
a. Undulating baseline refers to a regular pattern
of alternating tachycardia and bradycardia, often
with reduced variability between the wide swings
in heart rate.
b. Diminished or absent variability associated
with baseline FHR abnormalities. The ab-
sence of FHR variability is thought to be a result
of cerebral hypoxemia and acidosis, and signi-
fies failure of fetal compensatory mechanisms to
maintain adequate oxygenation of the brain.
c. Severe bradycardia with diminished variabil-
ity appears as a smooth FHR below 100 bpm
for a prolonged period of time (ie, at least 10
minutes). It is ominous when it occurs in the
absence of hypothermia, complete heart block,
or use of certain drugs (eg, beta-adrenergic
blockers, paracervical block).
d. Tachycardia with diminished variability appears
as a smooth FHR above 160 bpm. It is espe-
cially ominous when it occurs with late decelera-
tions or severe variable decelerations. Tachycar-
dia with normal variability and no decelerations,
tachycardia is unlikely to be related to
hypoxemia or acidosis. Possible causes include
fever, thyrotoxicosis, arrhythmia, maternal tachy-
cardia, and drugs.
e. Fetal neurological injury. The most common
FHR abnormality is a persistent nonreactive
heart rate, and a persistent fixed baseline with
minimal or absent variability.

National Institutes of Health guidelines for interpreta-

tion of fetal heart tracings
Variability
Absent = amplitude undetectable
Minimal = amplitude 0 to 5 bpm
Moderate = amplitude 6 to 25 bpm
Marked = amplitude over 25 bpm
There is no distinction between shortterm and longterm
variability
Baseline rate
Bradycardia = below 110 bpm
Normal = 110 to 160 bpm
Tachycardia = over 160 bpm
The baseline rate is the mean bpm (rounded to 0 or 5)
over a 10 minute interval, excluding periodic changes,
periods of marked variability, and segments that differ by
more than 25 bpm. The baseline must continue for 2
minutes during the interval, otherwise it is considered
indeterminate.
Acceleration
An abrupt increase in the FHR. Before 32 weeks of ges-
tation, accelerations should last >10 sec and peak >10
bpm above baseline. As of 32 weeks gestation, accelera-
tions should last >15 sec and peak >15 bpm above
baseline.
A prolonged acceleration is >2 minutes but less than 10
minutes. An acceleration of 10 minutes or more is con-
sidered a change in baseline.
Late deceleration
A gradual decrease and return to baseline of the FHR
associated with a uterine contraction. The deceleration is
delayed in timing, with the nadir of the deceleration oc-
curring after the peak of the contraction.
Early deceleration
A gradual decrease and return to baseline of the FHR
associated with a uterine contraction. The deceleration's
onset, nadir, and termination are coincident with the
onset, peak, and termination of the contraction.
Variable deceleration
An abrupt decrease in FHR below the baseline. The
>
decrease is 15 bpm, lasting >15 secs and <2 minutes
from onset to return to baseline. The onset, depth, and
duration of variable decelerations commonly vary with
successive uterine contractions.
Prolonged deceleration
 A decrease in FHR below the baseline of 15 bpm, lasting
2 minutes but <10 minutes from onset to return to base-
line. A prolonged deceleration of 10 minutes or more is
considered a change in baseline.

III. Overview of antepartum FHR monitoring

A. Antepartum FHR monitoring is performed in preg-
nancies in which the risk of fetal demise is known to
be increased.
B. Nonstress test (NST) is the most common
cardiotocographic method of antepartum fetal as-
sessment. There are no direct maternal or fetal risks
from nonstress testing.
1. Testing may be initiated when the fetal neurologi-
cal maturity enables FHR accelerations to occur,
typically at 26 to 28 weeks, and the fetus is be-
lieved to be at increased risk of death. Testing is
performed at daily to weekly intervals. The pres-
ence of a reassuring pattern indicates that there is
no fetal hypoxemia.
2. The test is reactive if there are two or more fetal
heart rate accelerations reaching a peak of 15
bpm above the baseline rate, and lasting for 15
seconds in a 20-minute period. A reactive test is
reassuring of fetal well-being. Reactivity prior to 32
weeks may be defined as two accelerations of at
least 10 beats per minute, lasting 10 seconds or
more, over a 20-minute interval.
3. A nonreactive NST is defined as one that does not
show such accelerations over a 40-minute period.
Nonreactivity may be a sign of fetal hypoxemia or
acidosis and is nonreassuring. Fetuses with a
nonreactive NST have a mean umbilical vein pH
of 7.28, while those with low biophysical profile
(BPP) scores have a mean pH of 7.16.
4. Management of the fetus with a nonreactive
NST. At term, delivery is usually indicated since
fetal hypoxemia cannot be definitively excluded
when the NST is nonreactive. A nonreassuring
NST in a preterm gestation poses a greater di-
lemma. Ancillary tests may prove useful in avoid-
ing a premature iatrogenic delivery, since the false
positive rate of an isolated nonreactive NST is 50
to 60%. Some options include:
a. Vibroacoustic stimulation.
b. Biophysical profile or Doppler velocimetry.
c. Modify factors potentially causing abnormal test
results, such as correction of diabetic
ketoacidosis or maternal hypotension.
5. Vibroacoustic stimulation is useful for decreas-
ing the number of nonreactive NSTs related to
quiet fetal sleep cycles. This test is performed by
placing an artificial larynx on the maternal abdo-
men and delivering a short burst of sound to the
fetus. The procedure shortens the duration of time
needed to produce an acceleration.
C. Contraction stress test (CST) is usually performed
using oxytocin. A dilute solution of oxytocin is infused
until three contractions occur within 10 minutes. Rela-
tive contraindications include preterm labor, patients
at high risk of preterm delivery, preterm premature
rupture of membranes, placenta previa, and previous
classical cesarean delivery or extensive uterine sur-
gery.
D. CST interpretation:
1. A positive (nonreassuring) test is defined by the
presence of late decelerations following 50% or
more of the contractions (such a test is considered
positive even if the contraction frequency is less
than three in 10 minutes).
2. A negative (reassuring) test has no late or signifi-
cant variable decelerations.
3. An equivocal-suspicious pattern consists of inter-
mittent late or significant variable decelerations,
while an equivocal-hyperstimulatory pattern refers
to fetal heart rate decelerations occurring with
contractions more frequent than every two min-
utes or lasting longer than 90 seconds.
4. An unsatisfactory test is one in which the tracing is
uninterpretable or contractions are fewer than
three in 10 minutes.
5. The CST is also interpreted as described above in
women who are having spontaneous contractions
of adequate frequency.
E. A positive (nonreassuring) CST may indicate de-
creased fetal reserve and correlates with a 20 to 40%
incidence of abnormal FHR patterns during labor. An
equivocal-suspicious test with repetitive variable
decelerations is also associated with abnormal FHR
patterns in labor, which are often related to cord
compression due to oligohydramnios.
IV. Delivery. After weighing the potential risks of fetal
hypoxemia versus the maternal and neonatal risks asso-
ciated with iatrogenic preterm birth, preterm delivery may
be indicated for nonreactive nonstress test results that
are persistent and have been confirmed by additional
tests of fetal well-being (eg, BPP).
A. At term, additional testing can be omitted since the
neonatal risk from delivery is small.
B. Depending on the FHR pattern, induction of labor
with continuous FHR and contraction monitoring may
be attempted in the absence of obstetrical contraindi-
cations. Repetitive late decelerations or severe vari-
able decelerations generally mandate expeditious
delivery by cesarean.
References: See page 208.

Antepartum Fetal Surveillance

I. Antepartum fetal surveillance techniques
A. Antepartum fetal surveillance should be initiated in
pregnancies when the risk of fetal demise is known to
be increased. These problems can include
antiphospholipid syndrome, chronic hypertension,
renal disease, systemic lupus erythematosus, or type 1
diabetes mellitus. Monitoring should also be initiated in
pregnancy-related conditions such as preeclampsia,
intrauterine growth restriction (IUGR), multiple gesta-
tion, or postterm pregnancy.
B. Antepartum fetal surveillance can include the
nonstress test (NST), BPP, oxytocin challenge test
(OCT), or modified BPP.
C. Nonstress test
1. A NST is performed using an electronic fetal moni-
tor. Testing is generally begun at 32 to 34 weeks.
Testing is performed at daily to weekly intervals as
long as the indication for testing persists.
2. The test is reactive if there are two or more fetal
heart rate accelerations of 15 bpm above the base-
line rate lasting for 15 seconds in a 20 minute pe-
riod. A nonreactive NST does not show such accel-
erations over a 40 minute period. Nonreactivity may
be related to fetal immaturity, a sleep cycle, drugs,
fetal anomalies, or fetal hypoxemia.
3. If the NST is nonreactive, it is considered
nonreassuring and further evaluation or delivery of
the fetus is indicated. At term, delivery rather than
further evaluation is usually warranted. A
nonreassuring NST preterm usually should be as-
sessed with ancillary tests, since the false positive
rate of an isolated NST may be 50 to 60%.
D. Fetal movement assessment (“kick counts”)
1. A decrease in the maternal perception of fetal
movement often precedes fetal death by several
days.
2. The woman lies on her side and counts distinct fetal
movements. Perception of 10 distinct movements in
a period of up to 2 hours is considered reassuring.
Once 10 movements have been perceived, the
count may be discontinued. In the absence of a
reassuring count, non stress testing is recom-
mended.

Indications for Antepartum Fetal Surveillance

Maternal Pregnancy complications

Antiphospholipid syndrome Preeclampsia
Poorly controlled Decreased fetal movement
hyperthyroidism Oligohydramnios
Hemoglobinopathies Polyhydramnios
Cyanotic heart disease Intrauterine growth restriction
Systemic lupus erythematosus Postterm pregnancy
Chronic renal disease Isoimmunization
Type I diabetes mellitus Previous unexplained fetal de-
Hypertensive disorders mise
Multiple gestation

Components of the Biophysical Profile

Parameter Normal (score = 2) Abnormal

(score = 0)

Nonstress >2 accelerations >15 <2 accelerations

test beats per minute above
baseline during test last-
ing >15 seconds in 20
minutes

Amniotic Amniotic fluid index >5 or AFI <5 or no

fluid volume at least 1 pocket measur- pocket >2 cm x
ing 2 cm x 2 cm in per- 2 cm
pendicular planes

Fetal breath- Sustained FBM (>30 Absence of FBM

ing move- seconds) or short gasps
ment only <30 sec-
onds total

Fetal body >3 episodes of either limb <3 episodes

movements or trunk movement during test

Fetal tone Extremities in flexion at Extension at rest

rest and >1 episode of or no return to
extension of extremity, flexion after
hand or spine with return movement
to flexion

A total score of 8 to 10 is reassuring; a score of 6 is suspicious,

and a score of 4 or less is ominous.
Amniotic fluid index = the sum of the largest vertical pocket in each
of four quadrants on the maternal abdomen intersecting at the
umbilicus.

E. Ancillary tests
1. Vibroacoustic stimulation is performed by placing
an artificial larynx on the maternal abdomen and
delivering a short burst of sound to the fetus. The
procedure can shorten the duration of time needed
to produce reactivity and the frequency of
nonreactive NSTs.
2. Oxytocin challenge test
a. The oxytocin challenge test (OCT) is done by
intravenously infusing dilute oxytocin until three
contractions occur within ten minutes. The test is
interpreted as follows:
(1) A positive test is defined by the presence of
late decelerations following 50% or more of
the contractions
(2) A negative test has no late or significant vari-
able decelerations
(3) An equivocal-suspicious pattern consists of
intermittent late or significant variable decel-
erations, while an equivocal-
hyperstimulatory pattern refers to fetal heart
rate decelerations occurring with contrac-
tions more frequent than every two minutes
or lasting longer than 90 seconds
b. An unsatisfactory test is one in which the tracing
is uninterpretable or contractions are fewer than
three in 10 minutes
c. A positive test indicates decreased fetal reserve
and correlates with a 20 to 40% incidence of
abnormal FHR patterns during labor. An
equivocal-suspicious test with repetitive variable
decelerations is also associated with abnormal
FHR patterns in labor, which are often related to
cord compression due to oligohydramnios.
3. Fetal biophysical profile
a. The fetal biophysical profile score refers to the
sonographic assessment of fetal movement,
fetal tone, fetal breathing, amniotic fluid volume
and nonstress testing. Each of these five param-
eters is given a score of 0 or 2 points. Fetal BPS
is a noninvasive, highly accurate means for pre-
dicting the presence of fetal asphyxia.
b. Criteria
(1) A normal variable is assigned a score of two
and an abnormal variable a score of zero.
The maximal score is 10/10 and the minimal
score is 0/10.
(2) Amniotic fluid volume is based upon an
ultrasound-based objective measurement of
the largest visible pocket. The selected larg-
est pocket must have a transverse diameter
of at least one centimeter.
c. Clinical utility
(1) The fetal BPS is noninvasive and highly ac-
curate for predicting the presence of fetal
asphyxia. The probability of fetal acidemia is
virtually zero when the score is normal (8 to
10). The false negative rate (ie, fetal death
within one week of a last test with a normal
score) is exceedingly low. The likelihood of
fetal compromise and death rises as the
score falls.
(2) The risk of fetal demise within one week of a
normal test result is 0.8 per 1000 women
tested. The positive predictive value of the
BPS for evidence of true fetal compromise is
only 50%, with a negative predictive value
>99.9%.
d. Indications and frequency of testing
(1) ACOG recommends antepartum testing
in the following situations:
(a) Women with high-risk factors for fetal
asphyxia should undergo antepartum
 fetal surveillance with tests (eg, BPS,
nonstress test)
(b) Testing may be initiated as early as 26
weeks of gestation when clinical condi-
tions suggest early fetal compromise is
likely. Initiating testing at 32 to 34 weeks
of gestation is appropriate for most preg-
nancies at increased risk of stillbirth.
(c) A reassuring test (eg, BPS of 8 to 10)
should be repeated periodically (weekly
or twice weekly) until delivery when the
high-risk condition persists.
(d) Any significant deterioration in the clinical
status (eg, worsening preeclampsia, de-
creased fetal activity) requires fetal re-
evaluation.
(e) Severe oligohydramnios (no vertical
pocket >2 cm or amniotic fluid index <5)
requires either delivery or close maternal
and fetal surveillance.
(f) Induction of labor may be attempted with
abnormal antepartum testing as long as
the fetal heart rate and contractions are
monitored continuously and are reassur-
ing. Cesarean delivery is indicated if
there are repetitive late decelerations.
(2) The minimum gestational age for testing
should reflect the lower limit that intervention
with delivery would be considered. This age
is now 24 to 25 weeks.
(3) Modified biophysical profile. Assessment
of amniotic fluid volume and nonstress test-
ing appear to be as reliable a predictor of
long-term fetal well-being as the full BPS.
The rate of stillbirth within one week of a
normal modified BPS is the same as with
the full BPS, 0.8 per 1000 women tested.

Guidelines for Antepartum Testing

Indication Initiation Frequency

Post-term pregnancy 41 weeks Twice a week

Preterm rupture of At onset Daily

membranes

Bleeding 26 weeks or at Twice a week

onset

Oligohydramnios 26 weeks or at Twice a week

onset

Polyhydramnios 32 weeks Weekly

Diabetes 32 weeks Twice a week

Chronic or 28 weeks Weekly. Increase

pregnancy-induced to twice-weekly at
hypertension 32 weeks.

Steroid-dependent or 28 weeks Weekly

poorly controlled
asthma

Sickle cell disease 32 weeks (ear- Weekly (more

lier if symptoms) often if severe)

Impaired renal func- 28 weeks Weekly

tion

Substance abuse 32 weeks Weekly

Prior stillbirth At 2 weeks be- Weekly

fore prior fetal
death

Multiple gestation 32 weeks Weekly

Congenital anomaly 32 weeks Weekly

Fetal growth restric- 26 weeks Twice a week or

tion at onset

Decreased fetal At time of com- Once

movement plaint

F. Perinatal outcome. An abnormal NST result should

be interpreted with caution. Further assessment of fetal
condition using the NST, OCT, or BPP should usually
be performed to help determine whether the fetus is in
immediate jeopardy.
G. Management of abnormal test results
1. Maternal reports of decreased fetal movement
should be evaluated by an NST, CST, BPP, or
modified BPP. These results, if normal, usually are
sufficient to exclude imminent fetal jeopardy. A
nonreactive NST or an abnormal modified BPP
generally should be followed by additional testing
(either a CST or a full BPP). In many circum-
stances, a positive CST result generally indicates
that delivery is appropriate.
2. A BPP score of 6 is considered equivocal; in the
term fetus, this score generally should prompt deliv-
ery, whereas in the preterm fetus, it should result in
a repeat BPP in 24 hours. In the interim, maternal
corticosteroid administration should be considered
for pregnancies of less than 34 weeks of gestation.
Repeat equivocal scores should result either in
delivery or continued intensive surveillance. A BPP
score of 4 usually indicates that delivery is war-
ranted.
3. Preterm delivery is indicated for nonreassuring
antepartum fetal testing results that have been
confirmed by additional testing. Depending on the
fetal heart rate pattern, induction of labor with con-
tinuous FHR and contraction monitoring may be
attempted in the absence of obstetrical contraindi-
cations. Repetitive late decelerations or severe
variable decelerations usually require cesarean
delivery.
References: See page 208.

Intrapartum Fetal Heart Rate Assess-

ment
Fetal heart rate (FHR) patterns are indirect indicators of the
fetal cardiac and medullary responses to blood volume
changes, academia, and hypoxemia. The FHR is determined
using a Doppler ultrasound device belted to the maternal
abdomen. A pressure transducer simultaneously monitors
the frequency, timing, and duration of uterine contractions.

I. Intrapartum FHR monitoring

A. Internal measurement of FHR is an invasive proce-
dure; thus, its use is restricted to the intrapartum pe-
riod. A bipolar spiral electrode is inserted
transcervically to penetrate the fetal scalp.
II. Further evaluation of nonreassuring tests
A. Transient episodes of hypoxemia, such as during a
contraction or temporary cord compression, are gener-
ally well-tolerated by the fetus. Repeated or prolonged
episodes, especially if severe, may lead to fetal acido-
sis and subsequent hypoxic-ischemic encephalopathy
(defined as metabolic acidosis pH <7, base deficit >12
mmol/L and Apgar score 0 to 3 for >5 minutes, and
evidence of neurologic sequelae).
B. One goal of intrapartum fetal surveillance is to distin-
guish the fetus with a nonreassuring FHR tracing who
is hypoxemic, but well compensated, from one who is
acidotic and at risk for neurologic impairment or death.
Further evaluation using ancillary tests are useful for
this purpose.
1. FHR response to stimulation. The examiner
stimulates the fetal vertex with the examining finger
during vaginal examination. If a FHR acceleration
is elicited, absence of acidosis (ie, fetal pH >7.20)
is likely. Vibroacoustic stimulation is a less invasive
technique. When accelerations are induced by
scalp stimulation, acidosis is present in less than
10% of fetuses, and when no accelerations occur,
acidosis is present in about 50% of fetuses.
2. Fetal scalp blood sampling. An amnioscope with
a light source is used to expose the fetal scalp. The
scalp is smeared with silicone gel so that a droplet
of blood forms when the scalp is punctured with a
2-mm blade. The blood is collected in long,
heparinized capillary tubes. The test requires that
the cervix be dilated at least 2 to 3 cm.
3. Capillary blood collected from the fetal scalp corre-
lates well with fetal arterial values. However, scalp
edema can result in erroneous results. A scalp pH
value of <7.20 is used to identify fetal acidosis.
4. Technical skill and parturient discomfort have pre-
cluded use of fetal blood sampling in many labor
and delivery units. Furthermore, the test has poor
sensitivity and positive predictive value (PPV) for
predicting umbilical arterial pH <7.0.
III. Management of nonreassuring FHR patterns
A. Determine the cause of the abnormality: Abruptio
placenta, cord prolapse, maternal medication (eg,
butorphanol, opiates, beta-mimetics).
B. Change maternal position from side to side, into
Trendelenburg, or to knee-elbow. This may dislodge
an occult cord prolapse. The supine position should be
avoided because of markedly reduced cardiac output
due to uterine compression of the vena cava.
C. Give an intravenous fluid bolus of nonglucose
crystalloid (eg, 1000 mL), unless there is volume
overload. This may improve placental blood flow if the
patient is intravascularly hypovolemic from prolonged
lack of intake, vomiting, or sympathetic blockade.
D. Discontinue oxytocin. Blood flow to the placenta is
reduced during contractions. Iatrogenic
hyperstimulation is a leading cause of nonreassuring
FHR tracings.
E. Perform a vaginal examination to check for a
prolapsed umbilical cord or rapid cervical dilatation
and descent of the fetal head.
F. If neuraxial anesthesia was recently administered,
check for maternal hypotension and ask the anesthesi-
ologist to evaluate the patient and administer ephed-
rine. Reduced perfusion of the placenta from sympa-
thetic blockade can occur without marked changes in
maternal blood pressure.
G. Administer oxygen by mask (10 L/min) to the mother
to improve fetal oxygenation.
H. Tocolysis with subcutaneous terbutaline 0.25 mg
should be initiated if uterine hypercontractility is pres-
ent (not secondary to oxytocin).
I. Amnioinfusion if there are persistent variable decel-
erations.
J. Ancillary tests to determine the fetal condition
should be completed if the nonreassuring pattern does
not resolve within a few minutes.
1. Digital or vibroacoustic stimulation should be
administered it accelerations are not observed.
Presence of accelerations almost always assures
the absence of fetal acidosis.
2. If accelerations cannot be elicited, further evalua-
tion by fetal scalp sampling for pH, lactate concen-
tration, or fetal ECG is indicated to help clarify the
fetal acid-base status. If accelerations cannot be
elicited, then variability should be evaluated. If vari-
ability is decreased in the setting of repetitive decel-
erations, delivery should be accomplished.
K. Determine whether operative intervention (cesar-
ean or instrumental vaginal delivery) is needed.
L. Expeditious delivery is indicated for persistent
nonreassuring FHR patterns associated with acidosis
or if the presence of acidosis cannot be excluded.

Management of Variant Fetal Heart Rate Patterns

FHR Pattern Diagnosis Action

Normal rate normal Fetus is well oxy- None

variability, accelera- genated
tions,
no decelerations

Normal variability, Fetus is still well Conservative man-

accelerations, mild oxygenated cen- agement.
nonreassuring pat- trally
tern (bradycardia,
late decelerations,
variable deceler-
ations)

Normal variability, ± Fetus is still well Continue conser-

accelerations, oxygenated cen- vative manage-
moderate-severe trally, but the FHR ment. Consider
nonreassuring pat- suggests hypoxia stimulation testing.
tern (bradycardia, Prepare for rapid
late decelerations, delivery if pattern
variable decelera- worsens
tions)

Decreasing vari- Fetus may be on Deliver if sponta-

ability, the verge of neous delivery is
± accelerations, decompensation remote, or if stimu-
moderate-severe lation supports
nonreassuring pat- diagnosis of
terns (bradycardia, decompensation.
late decelerations, Normal response
variable decelera- to stimulation may
tions) allow time to await
a vaginal delivery

Absent variability, Evidence of ac- Deliver. Stimula-

no accelerations, tual or impending tion
moderate/severe asphyxia or in-utero man-
nonreassuring pat- agement may be
terns (bradycardia, attempted if deliv-
late decelerations, ery is not delayed
variable deceler-
ations)

References: See page 208.

Brief Postoperative Cesarean Section
Note
Pre-op diagnosis:
1. 23 year old G1P0, estimated gestational age = 40
weeks
2. Dystocia
3. Non-reassuring fetal tracing
Post-op diagnosis: Same as above
Procedure: Primary low segment transverse cesarean
section
Attending Surgeon, Assistant:
Anesthesia: Epidural
Operative Findings: Weight and sex of infant, APGARs at 1
min and 5 min; normal uterus, tubes, ovaries.
Cord pH:
Specimens: Placenta, cord blood (type and Rh).
Estimated Blood Loss: 800 cc; no blood replaced.
Fluids, blood and urine output:
Drains: Foley to gravity.
Complications: None
Disposition: Patient sent to recovery room in stable condi-
tion.

Cesarean Section Operative Report

Preoperative Diagnosis:
1. 23 year old G1P0, estimated gestational age = 40
weeks
2. Dystocia
3. Non-reassuring fetal tracing
Postoperative Diagnosis: Same as above
Title of Operation: Primary low segment transverse cesar-
ean section
Surgeon:
Assistant:
Anesthesia: Epidural
Findings At Surgery: Male infant in occiput posterior pre-
sentation. Thin meconium with none below the cords, pediat-
rics present at delivery, APGAR's 6/8, weight 3980 g. Normal
uterus, tubes, and ovaries.
Description of Operative Procedure:
After assuring informed consent, the patient was taken to
the operating room and spinal anesthesia was initiated. The
patient was placed in the dorsal, supine position with left
lateral tilt. The abdomen was prepped and draped in sterile
fashion.
A Pfannenstiel skin incision was made with a scalpel and
carried through to the level of the fascia. The fascial incision
was extended bilaterally with Mayo scissors. The fascial
incision was then grasped with the Kocher clamps, elevated,
and sharply and bluntly dissected superiorly and inferiorly
from the rectus muscles.
The rectus muscles were then separated in the midline,
and the peritoneum was tented up, and entered sharply with
Metzenbaum scissors. The peritoneal incision was extended
superiorly and inferiorly with good visualization of the bladder.
A bladder blade was then inserted, and the vesicouterine
peritoneum was identified, grasped with the pick-ups, and
entered sharply with the Metzenbaum scissors. This incision
was then extended laterally, and a bladder flap was created.
The bladder was retracted using the bladder blade. The
lower uterine segment was incised in a transverse fashion
with the scalpel, then extended bilaterally with bandage
scissors. The bladder blade was removed, and the infants
head was delivered atraumatically. The nose and mouth
were suctioned and the cord clamped and cut. The infant
was handed off to the pediatrician. Cord gases and cord
blood were sent.
The placenta was then removed manually, and the uterus
was exteriorized, and cleared of all clots and debris. The
uterine incision was repaired with 1-O chromic in a running
locking fashion. A second layer of 1-O chromic was used to
obtain excellent hemostasis. The bladder flap was repaired
with a 3-O Vicryl in a running fashion. The cul-de-sac was
cleared of clots and the uterus was returned to the abdomen.
The peritoneum was closed with 3-0 Vicryl. The fascia was
reapproximated with O Vicryl in a running fashion. The skin
was closed with staples.
The patient tolerated the procedure well. Needle and
sponge counts were correct times two. Two grams of Ancef
was given at cord clamp, and a sterile dressing was placed
over the incision.
Estimated Blood Loss (EBL): 800 cc; no blood replaced
(normal blood loss is 500-1000 cc).
Specimens: Placenta, cord pH, cord blood specimens.
Drains: Foley to gravity.
Fluids: Input - 2000 cc LR; Output - 300 cc clear urine.
Complications: None.
Disposition: The patient was taken to the recovery room
then postpartum ward in stable condition.

Postoperative Management after Ce-

sarean Section
I. Post Cesarean Section Orders
A. Transfer: to post partum ward when stable.
B. Vital signs: q4h x 24 hours, I and O.
C. Activity: Bed rest x 6-8 hours, then ambulate; if given
spinal, keep patient flat on back x 8h. Incentive
spirometer q1h while awake.
D. Diet: NPO x 8h, then sips of water. Advance to clear
liquids, then to regular diet as tolerated.
E. IV Fluids: IV D5 LR or D5 ½ NS at 125 cc/h. Foley to
gravity; discontinue after 12 hours. I and O catheterize
prn.
F. Medications
1. Cefazolin (Ancef) 1 gm IVPB x one dose at time of
cesarean section.
2. Nalbuphine (Nubain) 5 to 10 mg SC or IV q2-3h OR
3. Meperidine (Demerol) 50-75 mg IM q3-4h prn pain.
4. Hydroxyzine (Vistaril) 25-50 mg IM q3-4h prn nau-
sea.
5. Prochlorperazine (Compazine) 10 mg IV q4-6h prn
nausea OR
6. Promethazine (Phenergan) 25-50 mg IV q3-4h prn
nausea
G. Labs: CBC in AM.
II. Postoperative Day #1
A. Assess pain, lungs, cardiac status, fundal height, lochia,
passing of flatus, bowel movement, distension, tender-
ness, bowel sounds, incision.
B. Discontinue IV when taking adequate PO fluids.
C. Discontinue Foley, and I and O catheterize prn.
D. Ambulate tid with assistance; incentive spirometer q1h
while awake.
E. Check hematocrit, hemoglobin, Rh, and rubella status.
F. Medications
1. Acetaminophen/codeine (Tylenol #3) 1-2 PO q4-6h
prn pain OR
2. Oxycodone/acetaminophen (Percocet) 1 tab q6h prn
pain.
3. FeSO4 325 mg PO bid-tid.
4. Multivitamin PO qd, Colace 100 mg PO bid. Mylicon
80 mg PO qid prn bloating.
III. Postoperative Day #2
A. If passing gas and/or bowel movement, advance to
regular diet.
B. Laxatives: Dulcolax supp prn or Milk of magnesia 30 cc
PO tid prn. Mylicon 80 mg PO qid prn bloating.
IV. Postoperative Day #3
A. If transverse incision, remove staples and place steri-
strips on day 3. If a vertical incision, remove staples on
post op day 5.
B. Discharge home on appropriate medications; follow up
in 2 and 6 weeks.

Laparoscopic Bilateral Tubal Ligation

Operative Report
Preoperative Diagnosis: Multiparous female desiring perma-
nent sterilization.
Postoperative Diagnosis: Same as above
Title of Operation: Laparoscopic bilateral tubal ligation with
Falope rings
Surgeon:
Assistant:
Anesthesia: General endotracheal
Findings At Surgery: Normal uterus, tubes, and ovaries.
Description of Operative Procedure
After informed consent, the patient was taken to the operat-
ing room where general anesthesia was administered. The
patient was examined under anesthesia and found to have a
normal uterus with normal adnexa. She was placed in the
dorsal lithotomy position and prepped and draped in sterile
fashion. A bivalve speculum was placed in the vagina, and the
anterior lip of the cervix was grasped with a single toothed
tenaculum. A uterine manipulator was placed into the
endocervical canal and articulated with the tenaculum. The
speculum was removed from the vagina.
An infraumbilical incision was made with a scalpel, then
while tenting up on the abdomen, a Verres needle was admit-
ted into the intraabdominal cavity. A saline drop test was
performed and noted to be within normal limits.
Pneumoperitoneum was attained with 4 liters of carbon dioxide.
The Verres needle was removed, and a 10 mm trocar and
sleeve were advanced into the intraabdominal cavity while
tenting up on the abdomen. The laparoscope was inserted and
proper location was confirmed. A second incision was made 2
cm above the symphysis pubis, and a 5 mm trocar and sleeve
were inserted into the abdomen under laparoscopic visualiza-
tion without complication.
A survey revealed normal pelvic and abdominal anatomy. A
Falope ring applicator was advanced through the second trocar
sleeve, and the left Fallopian tube was identified, followed out
to the fimbriated end, and grasped 4 cm from the cornual
region. The Falope ring was applied to a knuckle of tube and
good blanching was noted at the site of application. No bleed-
ing was observed from the mesosalpinx. The Falope ring
applicator was reloaded, and a Falope ring was applied in a
similar fashion to the opposite tube. Carbon dioxide was
allowed to escape from the abdomen.
The instruments were removed, and the skin incisions were
closed with #3-O Vicryl in a subcuticular fashion. The instru-
ments were removed from the vagina, and excellent
hemostasis was noted. The patient tolerated the procedure
well, and sponge, lap and needle counts were correct times
two. The patient was taken to the recovery room in stable
condition.
Estimated Blood Loss (EBL): <10 cc
Specimens: None
Drains: Foley to gravity
Fluids: 1500 cc LR
Complications: None
Disposition: The patient was taken to the recovery room in
stable condition.

Postpartum Tubal Ligation Operative

Report
Preoperative Diagnosis: Multiparous female after vaginal
delivery, desiring permanent sterilization.
Postoperative Diagnosis: Same as above
Title of Operation: Modified Pomeroy bilateral tubal ligation
Surgeon:
Assistant:
Anesthesia: Epidural
Findings At Surgery: Normal fallopian tubes bilaterally
Description of Operative Procedure:
After assuring informed consent, the patient was taken to
the operating room and spinal anesthesia administered. A
small, transverse, infraumbilical skin incision was made with a
scalpel, and the incision was carried down through the underly-
ing fascia until the peritoneum was identified and entered. The
left fallopian tube was identified, brought into the incision and
grasped with a Babcock clamp. The tube was then followed out
to the fimbria. An avascular midsection of the fallopian tube was
grasped with a Babcock clamp and brought into a knuckle. The
tube was doubly ligated with an O-plain suture and transected.
The specimen was sent to pathology. Excellent hemostasis
was noted, and the tube was returned to the abdomen. The
same procedure was performed on the opposite fallopian tube.
The fascia was then closed with O-Vicryl in a single layer.
The skin was closed with 3-O Vicryl in a subcuticular fashion.
The patient tolerated the procedure well. Needle and sponge
counts were correct times 2.
Estimated Blood Loss (EBL): <20 cc
Specimens: Segments of right and left tubes
Drains: Foley to gravity
Fluids: Input - 500 cc LR; output - 300 cc clear urine
Complications: None
Disposition: The patient was taken to the recovery room in
stable condition.

Prevention of D Isoimmunization
The morbidity and mortality of Rh hemolytic disease can be
significantly reduced by identification of women at risk for
isoimmunization and by administration of D immunoglobulin.
Administration of D immunoglobulin [RhoGAM, Rho(D)
immunoglobulin, RhIg] is very effective in the preventing
isoimmunization to the D antigen.

I. Prenatal testing
A. Routine prenatal laboratory evaluation includes ABO
and D blood type determination and antibody screen.
B. At 28-29 weeks of gestation woman who are D nega-
tive but not D isoimmunized should be retested for D
antibody. If the test reveals that no D antibody is pres-
ent, prophylactic D immunoglobulin [RhoGAM, Rho(D)
immunoglobulin, RhIg] is indicated.
C. If D antibody is present, D immunoglobulin will not be
beneficial, and specialized management of the D
isoimmunized pregnancy is undertaken to manage
hemolytic disease of the fetus and hydrops fetalis.
II. Routine administration of D immunoglobulin
A. Abortion. D sensitization may be caused by abortion.
D sensitization occurs more frequently after induced
abortion than after spontaneous abortion, and it occurs
more frequently after late abortion than after early
abortion. D sensitization occurs following induced
abortion in 4-5% of susceptible women. All
unsensitized, D-negative women who have an induced
or spontaneous abortion should be treated with D
immunoglobulin unless the father is known to be D
negative.
B. Dosage of D immunoglobulin is determined by the
stage of gestation. If the abortion occurs before 13
weeks of gestation, 50 mcg of D immunoglobulin pre-
vents sensitization. For abortions occurring at 13
weeks of gestation and later, 300-mcg is given.
C. Ectopic pregnancy can cause D sensitization. All
unsensitized, D-negative women who have an ectopic
pregnancy should be given D immunoglobulin. The
dosage is determined by the gestational age, as de-
scribed above for abortion.
D. Amniocentesis
1. D isoimmunization can occur after amniocentesis.
D immunoglobulin, 300 mcg, should be adminis-
tered to unsensitized, D-negative, susceptible pa-
tients following first- and second-trimester amnio-
centesis.
2. Following third-trimester amniocentesis, 300 mcg of
D immunoglobulin should be administered. If am-
niocentesis is performed and delivery is planned
within 48 hours, D immunoglobulin can be withheld
until after delivery, when the newborn can be tested
for D positivity. If the amniocentesis is expected to
precede delivery by more than 48 hours, the patient
should receive 300 mcg of D immunoglobulin at the
time of amniocentesis.
E. Antepartum prophylaxis
1. Isoimmunized occurs in 1-2% of D-negative women
during the antepartum period. D immunoglobulin,
administered both during pregnancy and
postpartum, can reduce the incidence of D isoim-
munization to 0.3%.
2. Antepartum prophylaxis is given at 28-29 weeks of
gestation. Antibody-negative, Rh-negative gravidas
should have a repeat assessment at 28 weeks. D
immunoglobulin (RhoGAM, RhIg), 300 mcg, is
given to D-negative women. However, if the father
of the fetus is known with certainty to be D negative,
antepartum prophylaxis is not necessary.
F. Postpartum D immunoglobulin
1. D immunoglobulin is given to the D negative mother
as soon after delivery as cord blood findings indi-
cate that the baby is Rh positive.
2. A woman at risk who is inadvertently not given D
immunoglobulin within 72 hours after delivery
should still receive prophylaxis at any time up until
two weeks after delivery. If prophylaxis is delayed, it
may not be effective.
3. A quantitative Kleihauer-Betke analysis should be
performed in situations in which significant maternal
bleeding may have occurred (eg, after maternal
abdominal trauma, abruptio placentae, external
cephalic version). If the quantitative determination is
thought to be more than 30 mL, D immune globulin
should be given to the mother in multiples of one
vial (300 mcg) for each 30 mL of estimated fetal
whole blood in her circulation, unless the father of
the baby is known to be D negative.
G. Abruptio placentae, placenta previa, cesarean
delivery, intrauterine manipulation, or manual re-
moval of the placenta may cause more than 30 mL
of fetal-to-maternal bleeding. In these conditions, test-
ing for excessive bleeding (Kleihauer-Betke test) or
inadequate D immunoglobulin dosage (indirect
Coombs test) is necessary.
References: See page 208.

Complications of Preg-
nancy
Nausea and Vomiting of Pregnancy
and Hyperemesis Gravidarum
Nausea and vomiting to affects about 70% to 85% of pregnant
women. Symptoms of nausea and vomiting of pregnancy
(NVP) are most common during the first trimester; however,
some women have persistent nausea for their entire preg-
nancy. Hyperemesis often occurs in association with high levels
of human chorionic gonadotropin (hCG), such as with multiple
pregnancies, trophoblastic disease, and fetal anomalies such
as triploidy.

Conditions that Predispose to Excessive Nausea

and Vomiting

Viral gastroenteritis
Gestational trophoblastic disease
Hepatitis
Urinary tract infection
Multifetal gestation
Gallbladder disease
Migraine

I. Treatment of nausea and vomiting of pregnancy

A. Patients should avoid odors or foods that seem to be
aggravating the nausea. Useful dietary modifications
include avoiding fatty or spicy foods, and stopping iron
supplements. Frequent small meals also may improve
symptoms. Recommendations include bland and dry
foods, high-protein snacks, and crackers at the bedside
to be taken first thing in the morning.
B. Cholecystitis, peptic ulcer disease, or hepatitis can cause
nausea and vomiting and should be excluded.
Gastroenteritis, appendicitis, pyelonephritis, and pancre-
atitis also should be excluded. Obstetric explanations for
nausea and vomiting may include multiple pregnancies
or a hydatidiform mole.
C. Non-pharmacologic remedies are adequate for up to
90% of patients with NVP. However, about 10% will
require medication and about 1% have severe enough
vomiting that they require hospitalization.
D. Vitamin therapy. Pyridoxine is effective as first-line
therapy and is recommended up to 25 mg three times
daily. Pyridoxine serum levels do not appear to correlate
with the prevalence or degree of nausea and vomiting.
Multivitamins also are effective for prevention of NVP.
Premesis Rx is a prescription tablet with controlled-
release vitamin B6, 75 mg, so it can be given once a day.
It also contains vitamin B12 (12 mcg), folic acid (1 mg),
and calcium carbonate (200 mg).
E. Over-the-Counter Therapy. If pyridoxine alone is not
efficacious, an alternative is to combine over-the-counter
doxylamine 25 mg (Unisom) and pyridoxine 25 mg. One
could combine the 25 mg of pyridoxine three times daily
with doxylamine 25 mg, 1 tablet every bedtime, and ½
tablet morning and afternoon. There is no evidence that
doxylamine is a teratogen.

Drug Therapy for Nausea and Vomiting of Preg-

nancy

Generic name (trade Dosage

name)

Antihistamines

Doxylamine (Unisom) 25 mg ½ tab BID, 1 tab qhs

Dimenhydrinate (Dramamine) 25 to 100 mg po/im/iv every 4

to 6 hr

Diphenhydramine (Benadryl) 25 to 50 mg po/im/iv every 4

to 6 hr

Trimethobenzamide (Tigan) 250 mg po every 6 to 8 hr or

200 mg im/pr every 6 to 8 hr

Meclizine (Antivert) 12.5 to 25 mg BID/TID

Phenothiazines

Promethazine (Phenergan) 12.5 to 25 mg po/iv/pr every 4

to 6 hr

Prochlorperazine (Compazine) 5 to 10 mg po/iv every 6 to 8

hr or
25 mg pr every 6 to 8 hr

Prokinetic agents

Metoclopramide (Reglan) 10 to 20 mg po/iv every 6 hr

Serotonin (5-HT3) antagonists

Ondansetron (Zofran) 8 mg po/iv every 8 hr

Corticosteroids

Methylprednisolone (Medrol) 16 mg po TID for 3 days then

½ dose every 3 days for 2 wks

F. Pharmacologic Therapy
1. Prescribed medication is the next step if dietary
modifications and vitamin B6 therapy with
doxylamine are ineffective. The phenothiazines are
safe and effective, and promethazine (Phenergan)
often is tried first. One of the disadvantages of the
phenothiazines is their potential for dystonic effects.
2. Metoclopramide (Reglan) is the antiemetic drug of
choice in pregnancy in several European countries.
There was no increased risk of birth defects.
3. Ondansetron (Zofran) has been compared with
promethazine (Phenergan), and the two drugs are
equally effective, but ondansetron is much more
expensive. No data have been published on first
trimester teratogenic risk with ondansetron.
II. Hyperemesis gravidarum
A. Hyperemesis gravidarum occurs in the extreme 0.5% to
1% of patients who have intractable vomiting. Patients
with hyperemesis have abnormal electrolytes, dehydra-
tion with high urine-specific gravity, ketosis and
acetonuria, and untreated have weight loss >5% of
body weight. Intravenous hydration is the first line of
therapy for patients with severe nausea and vomiting.
 Administration of vitamin B1 supplements may be
necessary to prevent Wernicke's encephalopathy.
References: See page 208.

Spontaneous Abortion
Abortion is defined as termination of pregnancy resulting in
expulsion of an immature, nonviable fetus. A fetus of <20
weeks gestation or a fetus weighing <500 gm is considered
an abortus. Spontaneous abortion occurs in 15% of all preg-
nancies.

I. Threatened abortion is defined as vaginal bleeding oc-

curring in the first 20 weeks of pregnancy, without the
passage of tissue or rupture of membranes.
A. Symptoms of pregnancy (nausea, vomiting, fatigue,
breast tenderness, urinary frequency) are usually pres-
ent.
B. Speculum exam reveals blood coming from the cervical
os without amniotic fluid or tissue in the endocervical
canal.
C. The internal cervical os is closed, and the uterus is soft
and enlarged appropriate for gestational age.
D. Differential diagnosis
1. Benign and malignant lesions. The cervix often
bleeds from an ectropion of friable tissue.
Hemostasis can be accomplished by applying pres-
sure for several minutes with a large swab or by
cautery with a silver nitrate stick. Atypical cervical
lesions are evaluated with colposcopy and biopsy.
2. Disorders of pregnancy
a. Hydatidiform mole may present with early preg-
nancy bleeding, passage of grape-like vesicles,
and a uterus that is enlarged in excess of that
expected from dates. An absence of heart tones
by Doppler after 12 weeks is characteristic.
Hyperemesis, preeclampsia, or hyperthyroidism
may be present. Ultrasonography confirms the
diagnosis.
b. Ectopic pregnancy should be excluded when
first trimester bleeding is associated with pelvic
pain. Orthostatic light-headedness, syncope or
shoulder pain (from diaphragmatic irritation) may
occur.
(1) Abdominal tenderness is noted, and pelvic
examination reveals cervical motion tender-
ness.
(2) Serum beta-HCG is positive.
E. Laboratory tests
1. Complete blood count. The CBC will not reflect
acute blood loss.
2. Quantitative serum beta-HCG level may be posi-
tive in nonviable gestations since beta-HCG may
persist in the serum for several weeks after fetal
death.
3. Ultrasonography should detect fetal heart motion
by 7 weeks gestation or older. Failure to detect fetal
heart motion after 9 weeks gestation should prompt
consideration of curettage.
F. Treatment of threatened abortion
1. Bed rest with sedation and abstinence from inter-
course.
2. The patient should report increased bleeding (>nor-
mal menses), cramping, passage of tissue, or fever.
Passed tissue should be saved for examination.
II. Inevitable abortion is defined as a threatened abortion
with a dilated cervical os. Menstrual-like cramps usually
occur.
A. Differential diagnosis
1. Incomplete abortion is diagnosed when tissue
has passed. Tissue may be visible in the vagina or
endocervical canal.
2. Threatened abortion is diagnosed when the inter-
nal os is closed and will not admit a fingertip.
3. Incompetent cervix is characterized by dilatation
of the cervix without cramps.
B. Treatment of inevitable abortion
1. Surgical evacuation of the uterus is necessary.
2. D immunoglobulin (RhoGAM) is administered to
Rh-negative, unsensitized patients to prevent
isoimmunization. Before 13 weeks gestation, the
dosage is 50 mcg IM; at 13 weeks gestation, the
dosage is 300 mcg IM.
III. Incomplete abortion is characterized by cramping,
bleeding, passage of tissue, and a dilated internal os with
tissue present in the vagina or endocervical canal. Pro-
fuse bleeding, orthostatic dizziness, syncope, and pos-
tural pulse and blood pressure changes may occur.
A. Laboratory evaluation
1. Complete blood count. CBC will not reflect acute
blood loss.
2. Rh typing
3. Blood typing and cress-matching.
4. Karyotyping of products of conception is com-
pleted if loss is recurrent.
B. Treatment
1. Stabilization. If the patient has signs and symp-
toms of heavy bleeding, at least 2 large-bore IV
catheters (<16 gauge) are placed. Lactate
Ringer’s or normal saline with 40 U oxytocin/L is
given IV at 200 mL/hour or greater.
2. Products of conception are removed from the
endocervical canal and uterus with a ring forceps.
Immediate removal decreases bleeding. Curet-
tage is performed after vital signs have stabilized.
3. Suction dilation and curettage
a. Analgesia consists of meperidine (Demerol),
35-50 mg IV over 3-5 minutes until the patient
is drowsy.
b. The patient is placed in the dorsal lithotomy
position in stirrups, prepared, draped, and se-
dated.
c. A weighted speculum is placed intravaginally,
the vagina and cervix are cleansed, and a
paracervical block is placed.
d. Bimanual examination confirms uterine position
and size, and uterine sounding confirms the
direction of the endocervical canal.
e. Mechanical dilatation is completed with dilators
if necessary. Curettage is performed with an 8
mm suction curette, with a single-tooth
tenaculum on the anterior lip of the cervix.
4. Post-curettage. After curettage, a blood count is
ordered. If the vital signs are stable for several
hours, the patient is discharged with instructions to
avoid coitus, douching, or the use of tampons for
2 weeks. Ferrous sulfate and ibuprofen are pre-
scribed for pain.
5. Rh-negative, unsensitized patients are given IM
RhoGAM.
6. Methylergonovine (Methergine), 0.2 mg PO q4h
for 6 doses, is given if there is continued moderate
bleeding.
IV. Complete abortion
A. A complete abortion is diagnosed when complete
passage of products of conception has occurred. The
uterus is well contracted, and the cervical os may be
closed.
B. Differential diagnosis
1. Incomplete abortion
2. Ectopic pregnancy. Products of conception
should be examined grossly and submitted for
pathologic examination. If no fetal tissue or villi are
observed grossly, ectopic pregnancy must be
excluded by ultrasound.
C. Management of complete abortion
1. Between 8 and 14 weeks, curettage is necessary
because of the high probability that the abortion
was incomplete.
2. D immunoglobulin (RhoGAM) is administered to
Rh-negative, unsensitized patients.
3. Beta-HCG levels are obtained weekly until zero.
Incomplete abortion is suspected if beta-HCG
levels plateau or fail to reach zero within 4 weeks.
V. Missed abortion is diagnosed when products of concep-
tion are retained after the fetus has expired. If products
are retained, a severe coagulopathy with bleeding often
occurs.
A. Missed abortion should be suspected when the preg-
nant uterus fails to grow as expected or when fetal
heart tones disappear.
B. Amenorrhea may persist, or intermittent vaginal
bleeding, spotting, or brown discharge may be noted.
C. Ultrasonography confirms the diagnosis.
D. Management of missed abortion
1. CBC with platelet count, fibrinogen level, partial
thromboplastin time, and ABO blood typing and
antibody screen are obtained.
2. Evacuation of the uterus is completed after fetal
death has been confirmed. Dilation and evacua-
tion by suction curettage is appropriate when the
uterus is less than 12-14 weeks gestational size.
3. D immunoglobulin (RhoGAM) is administered to
Rh-negative, unsensitized patients.
References: See page 208.

Urinary Tract Infections in Pregnancy

Urinary tract infection (UTI) is common in pregnancy. Al-
though asymptomatic bacteriuria occurs with similar fre-
quency in pregnant and nonpregnant women, bacteriuria
progresses to symptomatic infection more frequently during
pregnancy.
I. Incidence
A. The prevalence of asymptomatic bacteriuria in preg-
nant and nonpregnant women is 5 to 9%. If asymp-
tomatic bacteriuria is not treated, pyelonephritis will
develop in 20 to 40% of pregnant patients. This rate
of progression to symptomatic disease is three- to
fourfold higher than in nonpregnant women.
B. Microbiology. Escherichia coli is responsible for 60
to 90% of cases of asymptomatic bacteriuria, cystitis,
and pyelonephritis.
C. Asymptomatic Bacteriuria refers to the isolation of
>100,000 CFU of a single organism/mL from a
midstream-voided specimen in a woman without UTI
symptoms. It occurs in 5 to 9% of pregnancies, usu-
ally developing in the first month of gestation.
II. Diagnosis
A. A single clean-catch midstream urine culture detects
80% of patients with asymptomatic bacteriuria; two
such cultures approach the sensitivity of
catheterization (96%). A positive urine culture is >105
CFU/mL. Isolation of more than one species or the
presence of lactobacillus or propiobacterium indi-
cates a contaminated specimen.
B. Screening for asymptomatic bacteriuria is standard
practice at the first prenatal visit.
III. Treatment of asymptomatic bacteriuria
A. Amoxicillin-clavulanate (Augmentin) 500 mg PO BID
for three days.
B. Nitrofurantoin (Macrodantin) 50 mg PO QID for
seven days.
C. Cefixime (Suprax) 250 mg PO QD for three days.
D. Fosfomycin (Monural) 3 g PO as a single dose.
E. Relapse typically occurs in the first two weeks after
treatment. Such infections should be treated with two
weeks of oral antibiotics.
F. Suppressive therapy is recommended for women
with persistent bacteriuria (ie, >2 positive urine cul-
tures). Nitrofurantoin (Macrodantin) 50 to 100 mg
orally at bedtime, for the duration of the pregnancy is
one option, or cephalexin (Keflex) 250 to 500 mg
orally at bedtime. A culture for test of cure is obtained
one week after completion of therapy and then re-
peated monthly until completion of the pregnancy.
IV. Cystitis occurs in 0.3 to 1.3% of pregnant women. Bac-
teria are confined to the lower urinary tract in these pa-
tients.
A. Acute cystitis should be considered in any gravida
with frequency, urgency, dysuria, hematuria, or
suprapubic pain in the absence of fever and flank
pain. Urine culture with a CFU count >102/mL should
be considered positive on a midstream urine speci-
men with pyuria.
B. Empiric treatment regimens:
1. Nitrofurantoin (Macrodantin) 100 mg BID
2. Cephalexin (Keflex) 500 mg BID to QID
C. Each of these drugs is given for three to seven days.
D. Other regimens which have a broader spectrum of
activity include amoxicillin-clavulanate (Augmentin)
500 mg BID or 250 mg TID, trimethoprim-
sulfamethoxazole (Bactrim) 1 DS BID but not in the
third trimester of pregnancy, cefpodoxime proxetil
(Vantin) 100 mg BID, and cefixime (Suprax) 400 mg
QD. All of these drugs can be used for three to seven
days. Fluoroquinolones should be avoided in preg-
nancy.
E. Monthly urine cultures should be performed begin-
ning one to two weeks after completion of treatment.
V. Pyelonephritis complicates 1 to 2% of all pregnancies.
Risk factors include asymptomatic bacteriuria, previous
pyelonephritis, renal and collecting system anomalies, and
renal calculi.
A. Presentation consists of fever, chills, and
costovertebral angle tenderness. Other symptoms
include dysuria, nausea, vomiting, and respiratory
distress.
B. Urinalysis reveals one or two bacteria per high-power
field in an unspun catheterized specimen or 20 bacte-
ria per HPF in a spun specimen; white cell casts con-
firm the diagnosis. Urine culture and antimicrobial
susceptibility testing should be performed.
C. Blood cultures are positive in 10 to 20% of patients.
D. Outpatient treatment, with one of the above regi-
mens, may be considered in the absence of underly-
ing medical conditions, anatomic abnormalities, preg-
nancy complications, or signs of sepsis.
E. Inpatient treatment
1. Fluoroquinolones should not be used because of
adverse effects on growing cartilage. Parenteral
beta lactams or gentamicin are the preferred antibi-
otics. Symptoms that persist for more than 48
hours, despite intravenous antibiotic therapy, re-
quire further evaluation with a renal ultrasound to
assess for perinephric abscess or renal calculi.
 2. Intravenous treatment should continue until the
patient is afebrile for 48 hours. Inpatient therapy is
followed by oral antibiotics to complete 10 to 14
days of treatment.

Parenteral Regimens for Empiric Treatment of Acute

Pyelonephritis in Pregnancy

Antibiotic, dose Interval

Ceftriaxone, 1 g Q24 hours

Gentamicin, 1 mg/kg (+ Q8 hours

ampicillin)

Ampicillin, 1-2 g (plus Q6 hours

gentamicin)*

Ticarcillin-clavulanate Q8 hours
(Timentin) 3.2 g

Piperacillin-tazobactam Q8-12 hours

3.375 g*

Imipenem-cilastatin, 250- Q6-8 hours

500 mg

* Recommended regimen if enterococcus suspected

3. Low-dose antimicrobial prophylaxis, such as

nitrofurantoin (Macrodantin) 50 to 100 mg PO QHS
or cephalexin (Keflex) 250 to 500 mg PO QHS,
and periodic urinary surveillance for infection are
recommended for the remainder of the pregnancy.
References: See page 208.

Trauma During Pregnancy

Trauma is the leading cause of nonobstetric death in women
of reproductive age. Six% of all pregnancies are complicated
by some type of trauma.
I. Mechanism of injury
A. Blunt abdominal trauma
1. Blunt abdominal trauma secondary to motor vehicle
accidents is the leading cause of nonobstetric-re-
lated fetal death during pregnancy, followed by falls
and assaults. Uterine rupture or laceration,
retroperitoneal hemorrhage, renal injury and upper
abdominal injuries may also occur after blunt
trauma.
2. Abruptio placentae occurs in 40-50% of patients
with major traumatic injuries and in up to 5% of
patients with minor injuries.
3. Clinical findings in blunt abdominal trauma.
Vaginal bleeding, uterine tenderness, uterine con-
tractions, fetal tachycardia, late decelerations, fetal
acidosis, and fetal death.
4. Detection of abruptio placentae. Beyond 20
weeks of gestation, external electronic monitoring
can detect uterine contractile activity. The presence
of vaginal bleeding and tetanic or hypertonic con-
tractions is presumptive evidence of abruptio pla-
centae.
5. Uterine rupture
a. Uterine rupture is an infrequent but life-threaten-
ing complication. It usually occurs after a direct
abdominal impact.
b. Findings of uterine rupture range from subtle
(uterine tenderness, nonreassuring fetal heart
rate pattern) to severe, with rapid onset of mater-
nal hypovolemic shock and death.
6. Direct fetal injury is an infrequent complication of
blunt trauma.
a. The fetus is more frequently injured as a result of
hypoxia from blood loss or abruption.
b. In the first trimester the uterus is well protected
by the maternal pelvis; therefore, minor trauma
usually does not usually cause miscarriage in the
first trimester.
B. Penetrating trauma
1. Penetrating abdominal trauma from gunshot and
stab wounds during pregnancy has a poor progno-
sis.
2. Perinatal mortality is 41-71%. Maternal mortality is
less than 5%.
II. Major trauma in pregnancy
A. Initial evaluation of major abdominal trauma in
pregnant patients does not differ from evaluation of
abdominal trauma in a nonpregnant patient.
B. Maintain airway, breathing, and circulatory volume.
Two large-bore (14-16-gauge) intravenous lines are
placed.
C. Oxygen should be administered by mask or
endotracheal intubation. Maternal oxygen saturation
should be kept at >90% (an oxygen partial pressure
[pO2] of 60 mm Hg).
D. Volume resuscitation
1. Crystalloid in the form of lactated Ringer's or normal
saline should be given as a 3:1 replacement for the
estimated blood loss over the first 30-60 minutes of
acute resuscitation.
2. O-negative packed red cells are preferred if emer-
gent blood is needed before the patient's own blood
type is known.
3. A urinary catheter should be placed to measure
urine output and observe for hematuria.
E. Deflection of the uterus off the inferior vena cava and
abdominal aorta can be achieved by placing the patient
in the lateral decubitus position. If the patient must
remain supine, manual deflection of the uterus to the
left and placement of a wedge under the patient's hip or
backboard will tilt the patient.
F. Secondary survey. Following stabilization, a more
detailed secondary survey of the patient, including fetal
evaluation, is performed.
III. Minor trauma in pregnancy
A. Clinical evaluation
1. Pregnant patients who sustain seemingly minimal
trauma require an evaluation to exclude significant
injuries. Common "minor" trauma include falls, es-
pecially in the third trimester, blows to the abdomen,
and "fender benders" motor vehicle accidents.
2. The patient should be questioned about seat belt
use, loss of consciousness, pain, vaginal bleeding,
rupture of membranes, and fetal movement.
3. Physical examination
a. Physical examination should focus on upper
abdominal tenderness (liver or spleen damage),
flank pain (renal trauma), uterine pain (placental
abruption, uterine rupture), and pain over the
symphysis pubis (pelvic fracture, bladder lacera-
tion, fetal skull fracture).
b. A search for orthopedic injuries should be com-
pleted.
B. Management of minor trauma
1. The minor trauma patient with a fetus that is less
than 20 weeks gestation (not yet viable), with no
significant injury can be safely discharged after doc-
umentation of fetal heart rate. Patients with
potentially viable fetuses (over 20 weeks of gesta-
tion) require fetal monitoring, laboratory tests and
ultrasonographic evaluation.
2. A complete blood count, urinalysis (hematuria),
blood type and screen (to check Rh status), and
coagulation panel, including measurement of the
INR, PTT, fibrinogen and fibrin split products, should
be obtained. The coagulation panel is useful if any
suspicion of abruption exists.
3. The Kleihauer-Betke (KB) test
a. This test detects fetal red blood cells in the ma-
ternal circulation. A KB stain should be obtained
routinely for any pregnant trauma patient whose
fetus is over 12 weeks.
b. Regardless of the patient's blood type and Rh
status, the KB test can help determine if
fetomaternal hemorrhage has occurred.
c. The KB test can also be used to determine the
amount of Rho(D) immunoglobulin (RhoGAM)
required in patients who are Rh-negative.
d. A positive KB stain indicates uterine trauma, and
any patient with a positive KB stain should re-
ceive at least 24 hours of continuous uterine and
fetal monitoring and a coagulation panel.
4. Ultrasonography is less sensitive for diagnosing
abruption than is the finding of uterine contractions
on external tocodynamometry. Absence of
sonographic evidence of abruption does not com-
pletely exclude an abruption.
5. Patients with abdominal pain, significant bruising,
vaginal bleeding, rupture of membranes, or uterine
contractions should be admitted to the hospital for
overnight observation and continuous fetal monitor.
6. Uterine contractions and vaginal bleeding are sug-
gestive of abruption. Even if vaginal bleeding is
absent, the presence of contractions is still a con-
cern, since the uterus can contain up to 2 L of blood
from a concealed abruption.
7. Trauma patients with no uterine contraction activity,
usually do not have abruption, while patients with
greater than one contraction per 10 minutes (6 per
hour) have a 20% incidence of abruption.
References: See page 208.

Gestational Diabetes Mellitus

Gestational diabetes (GDM) occurs when pancreatic function
is not sufficient to overcome the insulin resistance caused by
diabetogenic hormones during pregnancy. Diabetogenic
hormones secreted by the placenta include growth hormone,
corticotropin-releasing hormone, placental lactogen, and
progesterone.

I. Pathophysiology
A. Gestational diabetes mellitus is defined as glucose
intolerance with onset during pregnancy. Most women
with GDM have glucose intolerance that begins in
pregnancy, but some may have type 2 diabetes that
was not diagnosed before pregnancy.
B. Adverse effects of GDM and hyperglycemia:
1. Preeclampsia
2. Polyhydramnios
3. Fetal macrosomia
4. Birth trauma
5. Operative delivery
6. Perinatal mortality
7. Neonatal metabolic complications (hypoglycemia,
hyperbilirubinemia, hypocalcemia, erythremia)
C. There is a 10% per year risk development of maternal
diabetes mellitus after a pregnancy with gestational
diabetes.
II. Prevalence rates are higher in African, Hispanic, Native
American, and Asian women than white women. The
prevalence of GDM is 1.4% of pregnancies.

Risk Factors for Gestational Diabetes

• A family history of diabetes, especially in first degree relatives

• Prepregnancy weight of 110% of ideal body weight (pregravid
weight more than 90 kg) or more or weight gain in early adult-
hood.
• Age >25 years
• A previous large baby (>9 pounds [4.1 kg])
• History of abnormal glucose tolerance
• Hispanic, African, Native American, South or East Asian, and
Pacific Island ancestry
• A previous unexplained perinatal loss or birth of a malformed
child
• The mother was large at birth (>9 pounds [4.1 kg])
• Polycystic ovary syndrome
• Glycosuria at the first prenatal visit
• Current use of glucocorticoids
• Pregnancy-related hypertension

III. Screening
A. Universal screening should be performed at 24 to 28
weeks. However, screening is done at the first prenatal
visit if there is a high degree of suspicion of type 2
diabetes (eg, obesity, personal history of GDM,
glycosuria, or family history of diabetes). Women with a
history of GDM have a 33 to 50% risk of recurrence.
B. Evaluation of any woman who has a random serum
glucose value above 200 mg/dL or a fasting serum
glucose value >126 mg/dL is unnecessary, because
these findings alone are diagnostic of diabetes, if con-
firmed on a subsequent day.
C. Screening is done with a 50-g oral glucose challenge
test. A 50-g oral glucose load is given without regard to
the time elapsed since the last meal and plasma or
serum glucose is measured one hour later; a value
>130 is considered abnormal.
D. Women with an abnormal value are then given a 100-
g, three hour oral glucose tolerance test (GTT).
IV. Diagnostic testing
A. Three hour oral GTT. GDM is present if two or more of
the following serum glucose values are met or ex-
ceeded:

Criteria for Gestational Diabetes with Three Hour

Oral Glucose Tolerance Test

Fasting >95 mg/dL

1 hour >180 mg/dL

2 hour >155 mg/dL

3 hour >140 mg/dL

Any two or more abnormal results are diagnostic of gesta-

tional diabetes.

B. One abnormal GTT value. Women with one abnormal

value on the oral GTT are more likely to deliver a
 macrosomic infant than women without GDM. Treat-
ment of women with one abnormal GTT value de-
creases the risk of a macrosomic infant.
V. Pregestational diabetes. Previously unrecognized type
1 or type 2 diabetes may be diagnosed as GDM during
pregnancy. Postpartum documentation of persistent
glucose intolerance suggests one of these diagnoses.
A. Fasting hyperglycemia at diagnosis of GDM is asso-
ciated with an increased risk of congenital anomalies
(4.8 versus 1.5% in nondiabetic women).
B. Clues to the presence of type 1 diabetes include:
1. GDM in lean women
2. Diabetic ketoacidosis during pregnancy
3. Severe hyperglycemia during pregnancy requiring
large doses of insulin
4. Postpartum hyperglycemia
VI. Treatment and course of gestational diabetes
mellitus
A. Identifying women with GDM is important because
appropriate therapy can decrease fetal and maternal
morbidity, particularly macrosomia. Treatment con-
sists of dietary therapy, self blood glucose monitoring,
and insulin if target blood glucose values are not met
with diet alone.
B. Treatment of GDM results in a significantly lower rate
of perinatal death, shoulder dystocia, bone fracture,
and nerve palsy, and a lower frequency of
macrosomia (10 versus 21%).
VII. Nutritional therapy
A. Calorie allotment is approximately:
1. 30 kcal per kg current weight per day in pregnant
women who are BMI 22 to 27.
2. 24 kcal per kg current weight per day in overweight
pregnant women (BMI 27 to 29).
3. 12 to 15 kcal per kg current weight per day for
morbidly obese pregnant women (BMI >30).
4. 40 kcal per kg current weight per day in pregnant
women who are less than BMI 22.
B. Carbohydrate intake is restricted to 35 to 40% of
calories, with the remainder divided between protein
(about 20%) and fat (about 40%).
VIII. Glucose monitoring
A. Timing and frequency. Blood glucose should be
measured upon awakening and one hour after each
meal.
B. Glucose goal. Insulin should be initiated if blood
glucose concentrations reach the following values on
two or more occasions within a two-week interval
despite dietary therapy:
1. Fasting blood glucose concentration >90 mg/dL.
2. One-hour postprandial blood glucose concentration
>120 mg/dL.
C. Glycosylated hemoglobin (HbA1c) is a helpful
ancillary test in assessing glycemic control during
pregnancy. HbA1c should be measured every four
weeks.
IX. Medical therapy. If normoglycemia cannot be main-
tained by nutritional therapy, then insulin should be initi-
ated.
A. Insulin. 15% of women with GDM are placed on
insulin because target glucose levels are exceeded
despite dietary therapy.
B. The dose of insulin ranges from 50 to 90 units to
achieve glucose control.
1. If fasting blood glucose concentration is high,
intermediate-acting NPH insulin is given before
bedtime. The initial dose is 0.2 U/kg body weight.
2. If postprandial blood glucose concentrations
are high, regular insulin or insulin lispro should be
given before meals at a dose calculated to be 1.5
U per 10 grams carbohydrate in the breakfast
meal and 1 U per 10 grams carbohydrate in the
lunch and dinner meals.
3. If both preprandial and postprandial blood
glucoses are high, then a four injection per day
regimen should be started. Total dosage should
be 0.7 U/kg up to week 18, 0.8 U/kg for weeks 18
to 26, 0.9 U/kg for weeks 26 to 36, and 1.0 U/kg
for weeks 36 to term.
4. The insulin is divided as 45% NPH insulin (30%
before breakfast and 15% before bedtime) and
55% as preprandial regular insulin (22% before
breakfast, 16.5% before lunch, and 16.5% before
dinner).
C. Acute hypoglycemia is treated with 10 to 20 g of
carbohydrate. One unit of rapid-acting insulin lowers
blood glucose by 25 mg/dL.
X. Peripartum management. Insulin can usually be with-
held during labor delivery; an infusion of normal saline is
usually sufficient to maintain normoglycemia. Maternal
blood glucose should be maintained between 70 and 90
mg/dL.
References: See page 208.

Management of Diabetes Mellitus in

Pregnancy
Management of diabetes mellitus in pregnancy has the goals
of achieving and maintaining excellent glycemic control and
intervention for maternal medical complications. Monitoring of
and intervention for fetal and obstetrical complications (eg,
congenital anomalies, preeclampsia, macrosomia) is essen-
tial.

I. First trimester
A. First prenatal visit. Pregestational diabetes can be
categorized as "vascular disease present" or "vascular
disease absent" because placental dysfunction and
aggravation of maternal end-organ disease are more
common in women with vasculopathy.
B. Testing. Routine prenatal laboratory evaluations are
performed. Treatment of asymptomatic bacteriuria is
important because there is a three- to five-fold greater
propensity for asymptomatic bacteriuria in diabetic
women.
1. Glycosylated hemoglobin concentration is ob-
tained for counseling regarding the risks of miscar-
riage and congenital malformations.
2. Quantification of urinary proteinuria should be
performed using the urinary protein-to-creatinine
ratio on a random urine sample.
3. Thyrotropin (TSH) and free thyroxine (T4). The
incidence of thyroid dysfunction in type I diabetes is
40%.
4. Electrocardiogram. Ischemic heart disease
should be screened for.
5. Dilated eye examination by an ophthalmologist to
detect retinopathy.
6. First trimester ultrasound examination should
be obtained to document viability and to assist in
estimation of gestational age.

Initial prenatal laboratory examination

Blood type and antibody screen

Rhesus type
Hematocrit or hemoglobin
Blood glucose
Creatinine
Free T4, TSH
Hemoglobin A1c
PAP smear
Rubella status (immune or nonimmune)
Syphilis screen
Urinalysis
Urinary protein-to-creatinine ratio
Hepatitis B surface antigen
HIV counseling and testing
Chlamydia
Electrocardiogram
Eye examination
Ultrasound

C. Management
1. Women receiving angiotensin converting enzyme
(ACE) inhibitors or receptor blockers (ARBs) for
hypertension or nephropathy should be taken off
these medications prior to pregnancy because of
teratogenicity.
2. Blood pressure should be maintained at 110 to 129
/65 to 79 mmHg in diabetic women with known
vascular disease. Antihypertensive therapy is with-
held when mild hypertension occurs in pregnant
women without vasculopathy because of lack of
proven benefit. Severe hypertension is treated to
prevent maternal stroke.
D. Second prenatal visit is scheduled about one week
after the first. Self-monitored blood glucose values
and results from the ophthalmologic and laboratory
examination (eg, renal function, glycosylated hemo-
globin, thyroid function) are reviewed.
E. Risk of congenital anomalies. A high risk of major
congenital malformations and miscarriage is associ-
ated with increasing first trimester glycosylated hemo-
globin values. A value >1% above the upper limit of
the normal range is associated with an increased risk
of congenital anomalies.
F. Aneuploidy testing with full integrated test. The full
integrated test consists of ultrasound measurement of
nuchal translucency thickness combined with a preg-
nancy-associated plasma protein-A at 10 to 13 weeks.

Frequency of Testing During Pregnancy in Women

with Type I Diabetes

Test Frequency

Hemoglobin Every 4-6 weeks

A1c

Blood glu- Home measurements 4-8 times daily;

cose during weekly/biweekly visits in physi-
cian’s office

Urine ke- During period of illness; when any blood

tones glucose value is >200 mg/dL

Urinalysis Weekly/biweekly office visits

Serum Each trimester

creatinine

Thyroid Baseline measurements of serum-free

function T4 and TSH
tests

Eye exami- Baseline and then every 3 months

nation

II. Second trimester

A. After the first two prenatal visits, which are scheduled
about one week apart, women are seen every two to
four weeks through the second trimester.
B. Quadruple markers should be obtained at 15 to 18
weeks, measuring alpha-fetoprotein (AFP),
unconjugated estriol (uE3), hCG, and inhibin A. The
prevalence of NTDs is higher in women with
pregestational diabetes mellitus. NTDs occur in 2%
of diabetic pregnancies versus 0.1 to 0.2% of the
general population. The median maternal serum
AFP (MSAFP) level is also 15% lower than in
nondiabetic women. For these reasons, a lower
threshold MSAFP value (eg, approximately 1.5 MoM)
is used in diabetic women.
1. Levels of MSAFP, unconjugated estriol (uE3), and
inhibin A are significantly reduced in women with
diabetes, thereby mimicking the pattern sugges-
tive of Down syndrome.
C. Ultrasound examination is obtained for the usual
obstetric indications. In addition, a level II ultrasound
examination is done at approximately 18 weeks of
gestation in pregnancies complicated by
pregestational diabetes because of the increased
prevalence of congenital anomalies. Biometric mea-
surements are obtained to confirm or revise the esti-
mated date of confinement.
D. The ultrasound examination should include a fetal
survey with a four-chamber view of the heart and
visualization of the outflow tracts. Congenital heart
disease occurs more frequently in the offspring of
diabetic women.
III. Third trimester
A. In the third trimester, diabetic gravida are typically
seen every one to two weeks until 32 weeks of gesta-
tion and then weekly until delivery.
1. Continued close monitoring of maternal blood
glucose levels
2. Avoidance of intrauterine fetal demise
3. Monitoring for obstetrical or medical complications
necessitating premature delivery
4. Detection of fetal macrosomia
B. Insulin resistance due to the hormones produced by
the placenta increases most rapidly during the third
trimester, changes in insulin dose are common at this
time.
C. Fetal surveillance. Antepartum monitoring using
fetal movement counting, biophysical profile,
nonstress test (NST), and/or contraction stress test is
initiated at 32 to 34 weeks of gestation.
D. Antepartum surveillance begins with weekly NSTs
at 32 weeks of gestation when there is suboptimal
glycemic control (glycosylated hemoglobin values
>7%) and at 34 to 35 weeks with good control
(glycosylated hemoglobin <7%), increasing the fre-
quency of testing to two times per week from 36
weeks until delivery.
E. Assessment of fetal growth. A sonogram is per-
formed at 38 weeks of gestation to estimate fetal
weight, reevaluate cardiac morphology, and assist
with delivery plans. Maternal diabetes can impair, but
more commonly accelerates, fetal growth. Ultrasound
examination should be done at 28 to 30 weeks to
assess fetal growth.
 F. Growth restriction. If there is evidence of
intrauterine growth restriction, which is uncommon
but often related to preeclampsia or preexisting ma-
ternal vasculopathy, tests of fetal well-being are initi-
ated.
G. Large for gestational age infants. A large for ges-
tational age (LGA) infant is defined as a fetal weight
>4.0 to 4.5 kg or birth weight above the 90th%ile for
gestational age. Maternal diabetes mellitus may
double the incidence of LGA infants.
1. LGA fetuses are at increased risk for a prolonged
second stage of labor, shoulder dystocia, opera-
tive delivery, birth trauma, and perinatal death.
Maternal diabetes mellitus increases the likelihood
of shoulder dystocia two- to six-fold.
2. Cesarean delivery is recommended for estimated
fetal weight over 4500 g.
H. Preeclampsia. The incidences of hypertension and
preeclampsia are increased in pregnant women with
diabetes. The incidence of preeclampsia in diabetic
women with and without vascular disease are 17 and
8%, respectively.
I. Polyhydramnios. Diabetic pregnancy is a common
etiology of polyhydramnios. Intervention is unneces-
sary because polyhydramnios related to diabetes is
usually mild.
J. Preterm labor. Women with pregestational diabetes
have higher rates of both indicated preterm delivery
(22%) and spontaneous preterm delivery (16%).
1. Tocolytic therapy should consist of nifedipine or
magnesium sulfate. Well-controlled diabetes
mellitus is not a contraindication to beta-
adrenergic receptor agonist therapy, as long as
glucose and potassium concentrations are fol-
lowed carefully and regulated.
2. Women with poorly controlled diabetes mellitus
should not receive beta-adrenergic receptor
agonists, which can cause severe hyperglycemia.
3. Betamethasone administration to reduce neona-
tal complications associated with preterm birth
should be done cautiously. Transient
hyperglycemia can be severe in the diabetic. The
hyperglycemic effect begins 12 hours after the first
dose and lasts for five days.
IV. Delivery
A. Fetal lung maturity. Respiratory distress syndrome
(hyaline membrane disease) is more likely to develop
in infants of diabetic mothers delivered early than in
infants of nondiabetic mothers. Maternal diabetes
delays fetal lung maturation.
1. Fetal lung maturity should be assessed with the
saturated phosphatidylcholine (SPC) in amniotic
fluid. An SPC >1000 mg/dL is required before
electively delivering a diabetic woman prior to 39
completed weeks.
2. RDS usually does not occur in any infant of a
diabetic mother delivered at or beyond 39 weeks
of gestation; assessment of fetal lung maturity is
not required at this gestational age.
B. Timing of delivery. Preterm delivery is generally
performed only for the usual obstetric indications (eg,
preeclampsia, fetal growth restriction, abruption,
premature labor with or without premature rupture of
membranes) or for worsening maternal renal or reti-
nal disease.
C. Labor should be induced at term (ie, between 39 and
40 completed weeks of gestation).
D. In women with an unfavorable cervix, induction
can be safely delayed until 40 and 0/7 weeks in
women with excellent glycemic control, no vascular
disease or preeclampsia, normal fetal growth, reas-
suring antepartum fetal surveillance, and no history of
stillbirth. If these criteria for continued pregnancy are
not met or the patient is not compliant, induction is
warranted before the cervix is favorable with cervical
ripening agents.
E. Route of delivery. Prophylactic cesarean delivery
may be considered to prevent brachial plexus injury
when the estimated fetal weight is >4500 g in a
woman with diabetes.
F. Labor and delivery. Peripartum maintenance of
maternal euglycemia is essential and generally re-
quires hourly capillary glucose determinations and
intravenous insulin infusion if hyperglycemia is pres-
ent.
V. Postpartum. Insulin requirements drop sharply after
delivery and should be recalculated based on serial
blood glucose determinations.
VI. Obstetrical management of gestational diabetes.
Women with GDM may have poor metabolic control and
macrosomic fetuses, which may affect the preferred
mode of delivery and neonatal outcome.
A. Fetal surveillance and timing of delivery. Women
with gestational diabetes who can maintain normal
blood sugars (fasting <105 mg/dL and two-hour post-
prandial <120 mg/dL) on a diabetic diet and have no
other pregnancy complications do not appear to be
at increased risk of stillbirth and probably do not re-
quire fetal surveillance.
B. Women with good glycemic control and no other
complications of pregnancy ideally will deliver at 39 to
40 weeks of gestation. If early delivery is indicated,
lung maturity should be assessed by amniocentesis if
delivery could be safely postponed in the absence of
fetal pulmonary maturity.
C. Intrapartum blood glucose control. The maternal
blood glucose concentration should be maintained
between 70 and 90 mg/dL. Insulin is rarely needed
during labor, and a normal saline infusion is usually
sufficient to maintain normoglycemia.
D. Postpartum follow-up. At 6 to 12 weeks
postpartum, women who had gestational diabetes
should be tested for type 2 diabetes.
References: See page 208.

Glycemic Control in Type 1 and Type

2 Diabetes Mellitus During Pregnancy
Diabetes in pregnancy can be classified as pregestational
diabetes if the diabetes was diagnosed before pregnancy, or
gestational diabetesif the diabetes was diagnosed during
pregnancy. Maintenance of maternal blood glucose at or
near normal decreases the occurrence of miscarriage, con-
genital anomalies, macrosomia, fetal death, and neonatal
morbidity.

I. Assessing glycemic control

A. Glycosylated hemoglobin values provide an assess-
ment of the degree of chronic glycemic control, reflect-
ing the mean blood glucose concentration during the
preceding six to eight weeks. An A1C level of 6%
correlates with an average glucose concentration of
120 mg/dL and each 1% increase in A1C reflects a 30
mg/dL increase in average glucose concentration.
1. A1C should be measured every four to six weeks.
The goal is to achieve a value at or near the normal
range (<6.1%) without inducing hypoglycemia. The
normal range of glucose concentration and A1C for
pregnant women is lower than that for nonpregnant
individuals since both average blood glucose con-
centration and A1C values fall by about 20% in
nondiabetic pregnant women. The goal is to achieve
A1C levels at, or ideally below, the normal range in
nonpregnant individuals.
B. Glucose monitoring. Self-glucose testing should be
done before and after meals, at bedtime, and occa-
sionally during the night if nocturnal hypoglycemia is
suspected. Peak postprandial glucose concentration
occurs 60 to 90 minutes after eating.
II. Target blood glucose values. Blood glucose goals in
pregnant diabetic women are:
A. Fasting blood glucose concentration of 55 to 65
mg/dL.
B. One-hour postprandial blood glucose concentration
less than 120 mg/dL.
III. Nutritional therapy
A. Calorie requirements during pregnancy are in-
creased by about 300 kcal above basal daily needs
in nonpregnant women. Recommended caloric in-
take:
1. 30 to 35 kcal per kg current weight per day in
pregnant women who are BMI 22 to 27.
2. 24 kcal per kg current weight per day in over-
weight pregnant women (BMI 27 to 29).
3. 12 to 15 kcal per kg current weight per day for
obese pregnant women (BMI >30).
4. 30 to 40 kcal per kg current weight per day in
pregnant women who are less than BMI 22.
IV. Insulin drug therapy
A. Most women with type 1 diabetes require at least
three injections of insulin per day. A two-injection
regimen can cause nocturnal hypoglycemia if the
action of evening-meal dose of intermediate-acting
insulin is maximal in the middle of the night.
B. Women with type 2 diabetes may achieve good
glycemic control with diet alone. Those who do not,
or are on oral anti-hyperglycemic agents, should be
treated with insulin for blood glucose control during
pregnancy. During the first trimester, insulin require-
ments are similar in women with type 1 and type 2
diabetes; however, in the second half of pregnancy,
insulin requirements increase proportionately more in
women with type 2 than type 1 diabetes; the respec-
tive insulin doses in the third trimester are1.6 and 1.2
U/kg per day for type 2 and type 1 diabetes, respec-
tively.
C. Lispro and aspart insulin analogs both improve
postprandial excursions compared to human regular
insulin and are associated with lower risk of delayed
postprandial hypoglycemia.
D. Human NPH insulin should be used as part of a
multiple injection regimen in pregnant women, and
women who were taking glargine prior to pregnancy
should be changed to NPH. A combination of lispro
or aspart insulin and NPH insulin is recommended
for therapy in pregnancy.
E. Regimen. After an early rise in insulin requirements
between weeks 3 and 7, there is a significant decline
between weeks 7 and 15 (hypoglycemia may occur),
followed by a rise during the remainder of pregnancy,
especially between weeks 28 and 32.
F. The average insulin requirement in pregnant women
with type 1 diabetes is 0.7 units/kg in the first trimes-
ter, increasing to 0.8 U/kg for weeks 13 to 28, 0.9
U/kg for weeks 29 to 34, and 1.0 U/kg for weeks 35
to term.
G. Meal related insulin lispro and aspart doses are 50%
of the insulin requirement. This dose is 0.15 times
their pregnant weight in kilograms (12 units of lispro
or aspart before meals). The other 50% of insulin
should cover basal needs. The dose is calculated as
0.45 times weight in kilograms (12 units of NPH three
times a day).
V. Intrapartum management
A. Spontaneous labor
1. Insulin is required during the latent phase of labor,
and can be given subcutaneously or by intrave-
nous infusion with a goal of maintaining glucose
between 70 and 90 mg/dL. Insulin infusion con-
sists of 15 units of regular insulin in 150 mL of
normal saline at a rate of 2-3 units/hour.
2. Normal saline may be sufficient to maintain
euglycemia when labor is anticipated.
3. During active labor, insulin resistance rapidly de-
creases and insulin requirements fall rapidly.
Thus, continuing insulin often causes
hypoglycemia. To prevent this, glucose should be
infused at a rate of 2.55 mg/kg per min. Capillary
blood glucose should be measured hourly.
4. Glucose, values of 120 mg/dL or greater require
rapid-acting insulin subcutaneously or regular
insulin intravenously until the blood glucose value
falls to 70 to 90 mg/dL. At this time, the insulin
dose is titrated to maintain normoglycemia while
glucose is infused at a rate of 2.55 mg/kg per min.
B. Cesarean delivery. The bedtime NPH insulin dose
may be given on the morning of surgery and every
eight hours thereafter if surgery is delayed.
C. Induction of labor. Women with type 1 and 2 diabe-
tes who receive labor induction should receive either
no morning insulin or a small dose of NPH insulin.
Blood glucose monitoring and glucose and insulin
infusion are managed as described above for spon-
taneous labor.

Low-dosage Constant Insulin Infusion for the

Intrapartum Period

Blood Glu- Insulin Dos- Fluids (125 mL/h)

cose (mg/100 age (U/h)
mL)

<100 0 5% dextrose solution

100-140 1.0 5% dextrose/solution

141-180 1.5 Normal saline

181-220 2.0 Normal saline

>220 2.5 Normal saline

Dilution is 15 U of regular insulin in 150 mL of normal saline, with

25 mL flushed through line, administered intravenously.

VI. Postpartum management. Insulin requirements drop

sharply after delivery, and the new mother may not re-
quire insulin for 24 to 72 hours. Insulin requirements
should be recalculated at this time at 0.6 units/kg per day
based upon postpartum weight. Postpartum calorie re-
quirements are 25 kcal/kg per day, and somewhat higher
(27 kcal/kg per day) in lactating women.
References: See page 208.
Group B Streptococcal Infection in
Pregnancy
Group B streptococcus (GBS; Streptococcus agalactiae), a
Gram positive coccus, is an important cause of infection in
neonates, causing sepsis, pneumonia, and meningitis. GBS
infection is acquired in utero or during passage through the
vagina. Vaginal colonization with GBS during pregnancy may
lead to premature birth, and GBS is a frequent cause of
maternal urinary tract infection, chorioamnionitis, postpartum
endometritis, and bacteremia.

I. Clinical evaluation
A. The primary risk factor for GBS infection is maternal
GBS genitourinary or gastrointestinal colonization.
B. The rate of transmission from colonized mothers to
infants is approximately 50%. However, only 1 to 2% of
all colonized infants develop early-onset GBS disease.
C. Maternal obstetrical factors associated with neo-
natal GBS disease:
1. Delivery at less than 37 weeks of gestation
2. Premature rupture of membranes
3. Rupture of membranes for 18 or more hours before
delivery
4. Chorioamnionitis
5. Temperature >38EC during labor
6. Sustained intrapartum fetal tachycardia
7. Prior delivery of an infant with GBS disease
D. Manifestations of early-onset GBS disease. Early-
onset disease results in bacteremia, generalized sep-
sis, pneumonia, or meningitis. The clinical signs usu-
ally are apparent in the first hours of life.
II. 2002 CDC guidelines for intrapartum antibiotic pro-
phylaxis:
A. All pregnant women should be screened for GBS
colonization with swabs of both the lower vagina and
rectum at 35 to 37 weeks of gestation. Patients are
excluded from screening if they had GBS bacteriuria
earlier in the pregnancy or if they gave birth to a previ-
ous infant with invasive GBS disease. These latter
patients should receive intrapartum antibiotic prophy-
laxis regardless of the colonization status.
B. Intrapartum antibiotic prophylaxis is recom-
mended for the following:
1. Pregnant women with a positive screening culture
unless a planned Cesarean section is performed in
the absence of labor or rupture of membranes
2. Pregnant women who gave birth to a previous in-
fant with invasive GBS disease
3. Pregnant women with documented GBS bacteriuria
during the current pregnancy
4. Pregnant women whose culture status is unknown
(culture not performed or result not available) and
who also have delivery at <37 weeks of gestation,
amniotic membrane rupture for >18 hours, or
intrapartum temperature >100.4ºF (>38ºC)
C. Intrapartum antibiotic prophylaxis is not recom-
mended for the following patients:
1. Positive GBS screening culture in a previous preg-
nancy (unless the infant had invasive GBS disease
or the screening culture is also positive in the cur-
rent pregnancy)
2. Patient who undergoes a planned Cesarean sec-
tion without labor or rupture of membranes
3. Pregnant women with negative GBS screening
cultures at 35 to 37 weeks of gestation even if they
have one or more of the above intrapartum risk
factors
D. Recommended IAP regimen
1. Penicillin G (5 million units IV initial dose, then 2.5
million units IV Q4h) is recommended for most
patients.
2. In women with non-immediate-type penicillin-
allergy, cefazolin (Ancef, 2 g initial dose, then 1 g
Q8h) is recommended.
3. Patients at high risk for anaphylaxis to penicil-
lins are treated with clindamycin (900 mg IV Q8h)
or erythromycin (500 mg IV Q6h) as long as their
GBS isolate is documented to be susceptible to
both clindamycin and erythromycin.
4. For patients at high risk for anaphylaxis and a
GBS resistant isolate (or with unknown suscepti-
bility) to clindamycin or erythromycin, vancomycin (1
g Q12h) should be given.
5. Antibiotic therapy is continued from hospital admis-
sion through delivery.
E. Approach to threatened preterm delivery at <37
weeks of gestation: A patient with negative GBS
cultures (after 35 weeks of gestation) should not be
treated during threatened labor. If GBS cultures have
not been performed, these specimens should be ob-
tained and penicillin G administered as above; if cul-
tures are negative at 48 hours, penicillin can be dis-
continued. If such a patient has not delivered within
four weeks, cultures should be repeated.
F. If screening cultures taken at the time of threat-
ened delivery or previously performed (after 35
weeks of gestation) are positive, penicillin should be
continued for at least 48 hours unless delivery super-
venes. Patients who have been treated for >48 hours
and have not delivered should receive IAP as above
when delivery occurs.
References: See page 208.

Premature Rupture of Membranes

Premature rupture of the membranes (PROM) refers to
rupture of membranes prior to the onset of labor or regular
uterine contractions. It can occur at term or prior to term, in
which case it is designated preterm premature rupture of the
membranes (PPROM). The frequencies of term, preterm,
and midtrimester PROM are 8, 1 to 3, and less than 1% of
pregnancies, respectively.
The incidence of this disorder to be 7-12%. In pregnancies of
less than 37 weeks of gestation, preterm birth (and its
sequelae) and infection are the major concerns after PROM.
I. Pathophysiology
A. Premature rupture of membranes is defined as
rupture of membranes prior to the onset of labor.
B. Preterm premature rupture of membranes is de-
fined as rupture of membranes prior to term.
C. Prolonged rupture of membranes consists of rup-
ture of membranes for more than 24 hours.
D. The latent period is the time interval from rupture of
membranes to the onset of regular contractions or
labor.
E. Many cases of preterm PROM are caused by idio-
pathic weakening of the membranes, many of which
are caused by subclinical infection. Other causes of
PROM include hydramnios, incompetent cervix,
abruptio placentae, and amniocentesis.
F. At term, about 8% of patients will present with ruptured
membranes prior to the onset of labor.
II. Maternal and neonatal complications
A. Labor usually follows shortly after the occurrence of
PROM. Ninety% of term patients and 50% of preterm
patients go into labor within 24 hours after rupture.
B. Patients who do not go into labor immediately are at
increasing risk of infection as the duration of rupture
increases. Chorioamnionitis, endometritis, sepsis, and
neonatal infections may occur.
C. Perinatal risks with preterm PROM are primarily com-
plications from immaturity, including respiratory dis-
tress syndrome, intraventricular hemorrhage, patent
ductus arteriosus, and necrotizing enterocolitis.
D. Premature gestational age is a more significant cause
of neonatal morbidity than is the duration of membrane
rupture.
III. Diagnosis of premature rupture of membranes
A. Diagnosis is based on history, physical examination,
and laboratory testing. The patient's history alone is
correct in 90% of patients. Urinary leakage or excess
vaginal discharge is sometimes mistaken for PROM.
B. Sterile speculum exam is the first step in confirming
the suspicion of PROM. Digital examination should be
avoided because it increases the risk of infection.
1. The general appearance of the cervix should be
assessed visually, and prolapse of the umbilical
cord or a fetal extremity should be excluded. Cul-
tures for group B streptococcus, gonorrhea, and
chlamydia are obtained.
2. A pool of fluid in the posterior vaginal fornix sup-
ports the diagnosis of PROM.
3. The presence of amniotic fluid is confirmed by
nitrazine testing for an alkaline pH. Amniotic fluid
causes nitrazine paper to turn dark blue because
the pH is above 6.0-6.5. Nitrazine may be false-
positive with contamination from blood, semen, or
vaginitis.
4. If pooling and nitrazine are both non-confirmatory, a
swab from the posterior fornix should be smeared
on a slide, allowed to dry, and examined under a
microscope for "ferning," indicating amniotic fluid.
5. Ultrasound examination for oligohydramnios is
useful to confirm the diagnosis, but oligohydramnios
may be caused by other disorders besides PROM.
C. Laboratory diagnosis
1. Alpha-fetoprotein (AFP) is present at high concen-
trations in amniotic fluid, but not in vaginal secre-
tions, urine, or semen.
2. Ultrasonography may be of value in the diagnosis
of PROM. The finding of anhydramnios or severe
oligohydramnios combined with a characteristic
history is highly suggestive, but not diagnostic, of
rupture of membranes.
3. Gestational age assessment should be calcu-
lated. Ultrasonography on admission is useful for
determining presentation, residual amniotic fluid
volume, fetal size and anatomic survey, and fetal
well-being.
4. Assessment of fetal well-being. Fetal well-being
is generally assessed via an external fetal monitor.
A reactive nonstress test is reassuring. Patients with
nonreassuring fetal heart rate testing should be
delivered or further evaluated.
IV. Assessment of premature rupture of membranes
A. The gestational age must be carefully assessed. Men-
strual history, prenatal exams, and previous
sonograms are reviewed. An ultrasound examination
should be performed.
B. The patient should be evaluated for the presence of
chorioamnionitis [fever (over 38EC), leukocytosis, ma-
ternal and fetal tachycardia, uterine tenderness, foul-
smelling vaginal discharge].
C. The patient should be evaluated for labor, and a sterile
speculum examination should assess cervical change.
D. The fetus should be evaluated with heart rate monitor-
ing because PROM increases the risk of umbilical cord
prolapse and fetal distress caused by oligohydramnios.
V. Management of premature rupture of membranes
A. Management of term patients
1. At 36 weeks and beyond, management of PROM
consists of delivery. Patients in active labor should
be allowed to progress.
2. Patients with chorioamnionitis, who are not in labor,
should be immediately induced with oxytocin (Pito-
cin).
3. Patients who are not yet in active labor (in the ab-
sence of fetal distress, meconium, or clinical infec-
tion) may be discharged for 48 hours, and labor
usually follows. If labor has not begun within a rea-
sonable time after rupture of membranes, induction
with oxytocin (Pitocin) is appropriate. Use of prosta-
glandin E2 is safe for cervical ripening.
B. Management of Preterm Premature Rupture of
Membranes
1. Women with PPROM should be hospitalized until
delivery. Expeditious delivery is indicated for
abruptio placentae, intrauterine infection, or evi-
dence of fetal compromise (eg, repetitive FHR de-
celerations or an unstable fetal presentation that
poses a risk of cord prolapse). Pregnancies >32
weeks of gestation with documented fetal lung ma-
turity will achieve better outcomes with immediate
delivery than with expectant management.
2. Group beta-hemolytic streptococcal (GBS) sta-
tus should be determined and intrapartum antibiotic
prophylaxis considered for pregnant women whose
GBS culture status is unknown (culture not per-
formed or result not available) and who also are
likely to deliver before 37 weeks of gestation, have
amniotic membranes that have been ruptured for
$18 hours, or have an intrapartum temperature
>100.4ºF.
3. Patients are typically kept at modified bedrest and
frequently assessed for evidence of infection or
labor.
4. Tocolytics can be given to allow administration of
antenatal corticosteroids and antibiotics.
5. Fetal surveillance consists of kick counts,
nonstress tests, biophysical profiles (BPP). Abnor-
malities of these tests are predictive of fetal infection
and umbilical cord compression related to
oligohydramnios.
6. Fetal lung maturity. Antenatal corticosteroid ad-
ministration is recommended for pregnancies com-
plicated by PPROM at less than 32 weeks of gesta-
tion, as long as there is no clinical evidence of
chorioamnionitis. A single course of corticosteroids
should be administered. In more advanced gesta-
tions, fetal lung maturity tests may be performed via
amniocentesis or on amniotic fluid samples aspi-
rated from the vagina.
7. All patients with PPROM should be delivered at >32
weeks after confirmation of fetal lung maturity or a
course of corticosteroids.
8. When there is confirmed fetal lung maturation at or
beyond 32 weeks of gestation, the risks of expec-
tant management often exceed those of delivery.
Women with PPROM who are >32 weeks of gesta-
tion with a mature fetal lung profile are best man-
aged by prompt induction of labor. Antibiotic pro-
phylaxis for possible GBS colonization should be
given during labor in the absence of a documented,
recent negative GBS culture.
9. Contraindications to expectant management.
Women are not candidates for expectant manage-
 ment if they have advanced labor, intrauterine infec-
tion, significant vaginal bleeding, or nonreassuring
fetal testing.
10. Antibiotic prophylaxis
a. Antibiotic therapy is important in the manage-
ment of patients with PPROM.
b. Ampicillin (1 or 2 g IV every 6 hours for 24 hours,
then 500 mg PO every 6 hours until delivery)
plus erythromycin or azithromycin is recom-
mended.
(1) Azithromycin (Zithromax, 1 g orally as a sin-
gle dose) may be substituted for
erythromycin because of improved oral ab-
sorption, a broader spectrum of antibacterial
properties, and better tolerance.
(2) Women with bacterial vaginosis should be
treated with metronidazole (250 mg PO
three times daily for seven days).

Sample Antibiotic Regimens Used for Prophylaxis in

Women with PPROM

Antibiotic Dose

Ampicillin 1 or 2 g IV every 6 hours for 24

hours, then 500 mg PO every 6
hours until delivery

Ampicillin 2 g IV every 6 hours for 4 doses and

Gentamicin 90 mg IV initially, then 60 mg IV every
8 hours for three doses and
Clindamycin 900 mg IV every 8 hours for three
doses, followed by
Amoxicillin plus 500 mg PO TID for 7 days
clavulanic acid
(Augmentin)

Erythromycin base 333 mg PO every 8 hours until deliv-

ery

Piperacillin 3 g IV every 6 hours for 3 days

Ampicillin-sulbactam 3 g every 6 hours for 7 days

(Unasyn)

Ampicillin 2 g IV every 6 hours for 7 days

Ampicillin-sulbactam 1.5 g IV every 6 hours for 72 hours,

Amoxicillin-clavulante followed by
500 mg PO every 8 hours until deliv-
ery

References: See page 208.

Preterm Labor and Delivery

Preterm birth (PTB) is defined as a birth that before 37 com-
pleted weeks (less than 259 days) of gestation. A very
preterm birth is defined as less than 32 weeks, and an ex-
tremely preterm birth is a birth at less than 28 weeks.
Preterm birth is the leading cause of infant mortality. 12.7%
of births are preterm and 2% are less than 32 weeks.

I. Pathogenesis. 70 to 80% of PTBs occur spontaneously:

preterm labor (PTL) accounts for 40 to 50% of all PTBs
and preterm premature rupture of membranes (PPROM)
accounts for 20 to 30%. The remaining 20 to 30% of
PTBs are due to intervention for maternal or fetal prob-
lems.
II. Clinical manifestations and diagnosis
A. 30% of preterm labors spontaneously resolve. 50%
of patients hospitalized for PTL deliver at term.
B. Signs and symptoms of early PTL include menstrual-
like cramping, constant low back ache, mild uterine
contractions at infrequent and/or irregular intervals,
and bloody show.
C. The diagnosis of PTL is generally based upon clinical
criteria of regular painful uterine contractions accom-
panied by cervical dilation and/or effacement. Spe-
cific criteria include persistent uterine contractions
(four every 20 minutes or eight every 60 minutes)
with documented cervical change or cervical efface-
ment of at least 80%, or cervical dilatation >2 cm.

Risk Factors for Preterm Labor

Previous preterm delivery Infectious causes

Low socioeconomic status --Chorioamnionitis
Non-white race --Bacterial vaginosis
Maternal age <18 years or --Asymptomatic bacteriuria
>40 years --Acute pyelonephritis
Preterm premature rupture of --Cervical/vaginal coloniza-
the membranes tion
Multiple gestation Fetal causes
Maternal history of one or --Intrauterine fetal death
more spontaneous --Intrauterine growth retar-
second-trimester abor- dation
tions --Congenital anomalies
Maternal complications Abnormal placentation
--Maternal behaviors Presence of a retained
--Smoking intrauterine device
--Illicit drug use
--Alcohol use
--Lack of prenatal care
Uterine causes
--Myomata (particularly
submucosal or
subplacental)
--Uterine septum
--Bicornuate uterus
--Cervical incompetence
--Exposure to diethylstil-
bestrol (DES)

D. Digital cervical examination has limited reproducibility

between examiners; therefore, evaluation of the cervix
via transvaginal ultrasound is useful to confirm the
diagnosis. Sonographic measurement of cervical
length is a more sensitive indicator of a patient's risk
for PTB than cervical dilatation. A short cervix has
been variously defined as a cervical length <2.0 cm.
III. Initial evaluation
A. Initial evaluation should address the following issues
1. The presence and frequency of uterine contrac-
tions
2. Uterine bleeding
3. Fetal membrane rupture
4. Gestational age
5. Fetal well-being
B. Uterine contractions and fetal well-being are evaluated
using an electronic fetal heart rate and contraction
monitor.
C. Physical examination. The uterus is examined to
assess firmness, tenderness, fetal size, and fetal
position. A sterile speculum examination is performed
to rule out ruptured membranes, to visually examine
the vagina and cervix, and to obtain specimens for
laboratory testing. A digital examination to assess
cervical dilatation and effacement is performed after
placenta previa and PPROM have been excluded (by
history and physical, laboratory, and ultrasound exam-
inations, as indicated).
D. Laboratory tests
1. Urine culture, since bacteriuria and pyelonephritis
are associated with PTB.
2. Rectovaginal group B streptococcal culture, to
determine need for antibiotic prophylaxis.
3. Tests for gonorrhea and chlamydia. Testing for
gonorrhea and chlamydia may be omitted if previ-
ously performed, the results were negative, and the
patient is not at high risk for sexually transmitted
infections.
4. Fetal fibronectin (fFN). A swab for fFN should be
obtained for all patients, but only send the swab to
the laboratory if the cervical length is 20 to 30 mm
5. Drug testing is indicated in patients with risk fac-
tors for drug abuse because cocaine use is associ-
ated with placental abruption.
6. Imaging. Ultrasound examination should be per-
formed to measure cervical length.

Preterm Labor, Threatened or Actual

IV. Initial assessment to determine whether patient is experienc-

ing preterm labor
A. Assess for the following:
1. Uterine activity
2. Rupture of membranes
3. Vaginal bleeding
4. Presentation
5. Cervical dilation and effacement
6. Station
B. Reassess estimate of gestational age
V. Search for a precipitating factor/cause
VI. Consider specific management strategies, which may include
the following:
A. Intravenous tocolytic therapy (decision should be influ-
enced by gestational age, cause of preterm labor and
contraindications)
B. Corticosteroid therapy (eg, betamethasone, in a dosage of
12 mg IM every 24 hours for a total of two doses)
C. Antibiotic therapy if specific infectious agent is identified or
if preterm premature rupture of the membranes

VII. Triage based upon cervical length

A. Cervical length >30 mm
1. These women are at low risk of PTB, regardless
of fFN result; therefore, fFN swabs do not need
to be sent to the laboratory. These patients
should be discharged home after an observa-
tional period of four to six hours during which fetal
well-being (eg, reactive nonstress test) should be
confirmed, and the presence of abruption or in-
fection should be excluded. The assessment
should confirm that the cervix is not dilating or
effacing.
2. Follow-up in one to two weeks is arranged and
the patient is given instructions to call if she expe-
riences additional signs or symptoms of PTL, or
has other pregnancy concerns (eg, bleeding,
PROM, decreased fetal activity).
B. Cervical length 20 to 30 mm. PTB is more likely in
women with cervices 20 to 30 mm than in women
with longer cervices, but most women in this group
do not deliver preterm. Therefore, the swab should
be sent for fFN testing in this subgroup of women. If
the test is positive (>50 ng/mL), the pregnancy
should be managed to prevent PTB.
C. Cervical length <20 mm. These women are at high
risk of PTB regardless of fFN result. Therefore, their
swabs should not be sent for fFN testing. Prevention
of PTB is indicated.
VIII. Management of women with preterm labor
A. Women diagnosed with PTL at less than 34 weeks
of gestation should be hospitalized, and the follow-
ing treatments should be initiated:
1. Antenatal glucocorticoids to reduce neonatal
morbidity and mortality associated with PTB.
2. Antibiotics for GBS chemoprophylaxis.
3. Tocolytic drugs for 48 hours to delay delivery so
that glucocorticoids given to the mother can
achieve their maximum effect.
4. Antibiotics to women with positive urine culture
results or positive tests for gonorrhea or
chlamydia.
IX. Inhibition of acute preterm labor
A. Goals of treatment of preterm labor
1. Delay delivery by at least 48 hours so that
glucocorticoids given to the mother can achieve
their maximum effect. Predelivery administration
of glucocorticoids reduces the risk of neonatal
death, respiratory distress syndrome,
intraventricular hemorrhage, and necrotizing
enterocolitis in premature neonates.
2. Provide time to transport the mother to a facility
that can provide neonatal care if the patient deliv-
ers preterm.
3. Prolong pregnancy when there are underlying,
self-limited conditions that can cause labor (such
as pyelonephritis) and are unlikely to cause re-
current PTL.
B. Lower and upper limits of gestational age. The low-
est gestational age for which inhibition of PTL
should be considered is fifteen weeks gestational
age since it defines a point at which early pregnancy
loss is less commonly attributable to karyotypic ab-
normality.
C. Thirty-four weeks of gestation defines the threshold
at which perinatal morbidity and mortality are felt to
be too low to justify the potential complications asso-
ciated with the inhibition of labor.
D. Contraindications to inhibition of labor
1. Intrauterine fetal demise
2. Lethal fetal anomaly
3. Nonreassuring fetal status
4. Severe fetal growth restriction
5. Severe preeclampsia or eclampsia
6. Maternal hemorrhage with hemodynamic instabil-
ity
7. Chorioamnionitis
E. Bedrest, hydration, and sedation is recom-
mended even though there is no high quality evi-
dence of the efficacy of bedrest for prevention or
treatment of PTL.
F. Beta-adrenergic receptor agonists
1. Mechanism of action. Terbutaline causes
myometrial relaxation by binding with beta-2
adrenergic receptors and increasing intracellular
adenyl cyclase, resulting in diminished
myometrial contractility. Target cells eventually
become desensitized to the effect of beta-
adrenergic receptor agonists, thereby limiting
efficacy because of tachyphylaxis.
2. Efficacy
a. Beta-adrenergic receptor agonists decreased
the number of women giving birth within 48
hours (RR 0.63 and possibly within seven
days (RR 0.67).
3. Maternal side effects include tachycardia, palpita-
tions, and lower blood pressure.
 a. Common symptoms include tremor (39%),
palpitations (18%), shortness of breath (15%),
and chest discomfort (10%).
b. Pulmonary edema is uncommon, occurring in
0.3% of patients.
c. Beta-adrenergic receptor agonists effects,
include hypokalemia (39%), hyperglycemia
(30%), and lipolysis. Myocardial ischemia is a
rare complication.
4. Fetal side effects, such as fetal tachycardia.
Neonatal hypoglycemia may result from fetal
hyperinsulinemia due to prolonged maternal
hyperglycemia.
5. Contraindications. Labor inhibition with a beta-
adrenergic receptor agonist is relatively contrain-
dicated among women with cardiac disease,
poorly controlled hyperthyroidism or diabetes
mellitus.
6. Dose
a. Terbutaline is the most commonly used beta-
adrenergic receptor agonist for labor inhibition.
It is typically administered as a continuous
intravenous infusion. The infusion is started at
2.5 to 5 mcg/min; this can be increased by 2.5
to 5 mcg/min every 20 to 30 minutes to a
maximum of 25 mcg/min, or until the contrac-
tions have abated. At this point, the infusion is
reduced by decrements of 2.5 to 5 mcg/min to
the lowest dose that maintains uterine quies-
cence.
b. Terbutaline can also be given subcutaneously
by intermittent injection. 0.25 mg can be ad-
ministered every 20 to 30 minutes for up to
four doses or until tocolysis is achieved. Once
labor is inhibited, 0.25 mg can be adminis-
tered every three to four hours until the uterus
is quiescent for 24 hours.
G. Monitoring.
1. During beta-adrenergic receptor agonist adminis-
tration, cumulative fluid intake, urine output,
shortness of breath, chest pain or tachycardia
should be monitored. The drug be withheld if the
maternal heart rate exceeds 120 beats/min.
2. Glucose and potassium concentrations
should be monitored every four to six hours dur-
ing parenteral drug administration, since
hyperglycemia and hypokalemia commonly oc-
cur. Significant hypokalemia should be treated to
minimize risk of arrhythmias.
H. Magnesium sulfate
1. Mechanism of action. Magnesium competes
with calcium at the level of the plasma mem-
brane voltage-gated channels, reducing
myometrial contractility.
2. Efficacy. Compared to no treatment or placebo,
magnesium sulfate therapy did not significantly
reduce the risk of birth within 48 hours (RR 0.57).
In comparative trials, magnesium sulfate was
neither more nor less effective than other
tocolytics.
3. Maternal side effects. Magnesium sulfate
causes fewer minor maternal side effects than
beta-adrenergic agonists, but the risk of major
adverse risk events is comparable. Rapid infu-
sion causes diaphoresis, flushing, and warmth.
Nausea, vomiting, headache, visual distur-
bances, and palpitations can also occur.
Dyspnea or chest pain may be symptoms of
pulmonary edema, which is a rare complication.
a. Magnesium toxicity: loss of deep tendon
reflexes occurs at 9.6 to 12.0 mg/dL, respira-
tory paralysis at 12.0 to 18.0 mg/dL, and car-
diac arrest at 24 to 30 mg/dL. Symptoms will
resolve after the magnesium infusion is
stopped. Calcium gluconate (1 g intravenously
over 5 to 10 minutes) should be administered
only to counteract life-threatening symptoms
of magnesium toxicity (such as
cardiorespiratory compromise).
b. Magnesium therapy also results in a transient
reduction of serum calcium concentration due
to rapid suppression of parathyroid hormone
release. Rarely, the hypocalcemia becomes
symptomatic (myoclonus, delirium, ECG ab-
normalities).
4. Contraindications. Magnesium sulfate tocolysis
is contraindicated in women with myasthenia
gravis. It also should not be used in women with
known myocardial compromise or cardiac con-
duction defects because of its antiinotropic ef-
fects.
a. Magnesium is eliminated by the kidneys.
Thus, women with impaired renal function will
have an exaggerated rise in serum magne-
sium and may develop magnesium toxicity.
5. Dose. Magnesium sulfate is usually administered
as a 4 to 6 g intravenous load over 20 minutes,
followed by a continuous infusion of 2 to 4 g/hour.
6. Monitoring. Since magnesium sulfate is ex-
creted by the kidneys, dosing should be reduced
in renal insufficiency (creatinine >1.0
mg/dL).Women with renal insufficiency should
receive a standard loading dose, but a reduced
maintenance dose (1 g per hour or no mainte-
nance dose if the serum creatinine is >2.5
mg/dL) with monitoring of the serum magnesium
every six hours.
I. Calcium channel blockers
1. Mechanism of action. Calcium channel
blockers directly block the influx of calcium ions
through the cell membrane, resulting in
myometrial relaxation.
2. Efficacy
a. Compared to other tocolytics, calcium channel
blockers did not significantly reduce the risk of
birth within 48 hours of initiation of treatment
(RR 0.80), but did reduce the risk of birth
within seven days (RR 0.76).
b. Comparing treatment of PTL with nifedipine
versus beta-adrenergic receptor agonists
(terbutaline). Nifedipine was more effective
than beta-adrenergic receptor agonists for
delaying delivery at least 48 hours (OR 1.52).
3. Maternal side effects. Nifedipine is a peripheral
vasodilator, thus it may cause symptoms such as
nausea, flushing, headache, dizziness, and palpi-
tations.
4. Contraindications. Calcium channel blockers
should be used with caution in women with left
ventricular dysfunction or congestive heart failure.
5. Dose. Administer an initial loading dose of 30 mg
orally, followed by an additional 20 mg orally in
90 minutes. The half-life of nifedipine is 2-3 hours
and the duration of action is up to six hours.

Tocolytic Therapy for the Management of Preterm

Labor

Medica- Mechanism of
tion action Dosage

Nifedipin Calcium channel 30 mg orally, followed by

e blocker 20 mg orally in 90 min-
(Procard utes, followed by 20 mg
ia) orally every four to eight
hours.

Terbutali Beta2-adrenergic 2.5 to 5 µg/min; in-

ne receptor agonist creased by 2.5 to 5
(Bricanyl sympathomimetic µg/min every 20 to 30
) ; decreases free minutes to a maximum of
intracellular cal- 25 µg/min, or until the
cium ions contractions have abated.
0.25 mg subcutaneously
every 20 to 30 minutes for
up to four doses or until
tocolysis is achieved. 0.25
mg every 3 to 4 hours.

Indomet Prostaglandin 50- to 100-mg rectal sup-

hacin inhibitor pository, then 25 to 50 mg
(Indocin) orally every six hours

Complications Associated With the Use of Tocolytic

Agents

Beta-adrenergic agents Indomethacin (Indocin)

• Hypokalemia
• Hyperglycemia
• Hypotension
• Pulmonary edema
• Arrhythmias
• Cardiac insufficiency
• Myocardial ischemia
• Maternal death
• Renal failure
• Hepatitis
• Gastrointestinal bleed-
ing
Nifedipine (Procardia)
• Transient hypotension

J. Cyclooxygenase inhibitors
1. Mechanism of action. Cyclooxygenase (COX) is
the enzyme responsible for conversion of
arachidonic acid to prostaglandins, which are
critical in parturition.
2. Efficacy
a. Indomethacin, a nonspecific COX inhibitor, is
the most commonly used tocolytic of this class.
COX inhibition showed a trend in reduction in
risk of delivery within 48 hours of initiation of
treatment (RR 0.20) and within seven days
(RR 0.41).
b. Indomethacin is significantly more effective
than placebo in inhibition of PTL during a 24-
hour course of therapy.
3. Maternal side effects, including nausea, esopha-
geal reflux, gastritis, and emesis, are seen in 4%
of patients treated with indomethacin for PTL.
Platelet dysfunction may occur.
4. Fetal side effects. The primary fetal concerns
with use of indomethacin, and other COX inhibi-
tors (eg, sulindac), are constriction of the ductus
arteriosus and oligohydramnios.
a. Ductus arteriosus. Premature narrowing or
closure of the ductus arteriosus can lead to
pulmonary hypertension, tricuspid regurgitation,
and persistent fetal circulation. Several cases
of premature ductal closure have been re-
ported in pregnancies in which the duration of
indomethacin exposure exceeded 48 hours.
b. Oligohydramnios. Indomethacin causes a
reduction in amniotic fluid volume. Fetal urine
output is reduced.
c. Other. Neonatal complications associated with
in-utero indomethacin exposure include
bronchopulmonary dysplasia, necrotizing
enterocolitis, patent ductus arteriosus, and
intraventricular hemorrhage.
5. Contraindications. Maternal contraindications to
COX inhibitors include platelet dysfunction or
bleeding disorder, hepatic dysfunction, gastroin-
testinal ulcerative disease, renal dysfunction, and
asthma.
6. Dose. Indomethacin is given as a 50 to 100 mg
loading dose, followed by 25 mg orally every four
to six hours.
7. Monitoring. If indomethacin is continued for lon-
ger than 48 hours, sonographic evaluation for
oligohydramnios and narrowing of the fetal ductus
arteriosus is indicated. Evidence of
oligohydramnios or ductal constriction should
prompt discontinuation of this therapy.
X. Recommendations
A. Nifedipine is the initial choice for tocolysis because of
oral administration, low frequency of side effects, and
efficacy in reducing neonatal morbidity.
B. Beta-adrenergic receptor agonists are also effective
agents for initial treatment of PTL, but have a high
rate of side effects.
C. For second line treatment of PTL in pregnancies
under 32 weeks of gestation, indomethacin should
be intitiated. These agents should be avoided in
gestations over 32 weeks and should be used with
caution if needed for more than 72 hours because of
concern about premature narrowing or closure of the
ductus arteriosus. For second line therapy of preg-
nancies at 32 to 34 weeks of gestation, beta-
adrenergic receptor agonists are recommended.
References: See page 208.

Bleeding in the Second Half of Preg-

nancy
Bleeding in the second half of pregnancy occurs in 4% of all
pregnancies. In 50% of cases, vaginal bleeding is secondary
to placental abruption or placenta previa.

I. Clinical evaluation of bleeding second half of preg-

nancy
A. History of trauma or pain and the amount and charac-
ter of the bleeding should be assessed.
B. Physical examination
1. Vital signs and pulse pressure are measured.
Hypotension and tachycardia are signs of serious
hypovolemia.
2. Fetal heart rate pattern and uterine activity are as-
sessed.
3. Ultrasound examination of the uterus, placenta and
fetus should be completed.
4. Speculum and digital pelvic examination should not
be done until placenta previa has been excluded.
C. Laboratory Evaluation
1. Hemoglobin and hematocrit.
2. INR, partial thromboplastin time, platelet count,
fibrinogen level, and fibrin split products are
checked when placental abruption is suspected or if
there has been significant hemorrhage.
3. A red-top tube of blood is used to perform a bed-
side clot test.
4. Blood type and cross-match.
5. Urinalysis for hematuria and proteinuria.
6. The Apt test is used to distinguish maternal or fetal
source of bleeding. (Vaginal blood is mixed with an
 equal part 0.25% sodium hydroxide. Fetal blood
remains red; maternal blood turns brown.)
7. Kleihauer-Betke test of maternal blood is used to
quantify fetal to maternal hemorrhage.
II. Placental abruption (abruptio placentae) is defined as
complete or partial placental separation from the decidua
basalis after 20 weeks gestation.
A. Placental abruption occurs in 1 in 100 deliveries.
B. Factors associated with placental abruption
1. Preeclampsia and hypertensive disorders
2. History of placental abruption
3. High multiparity
4. Increasing maternal age
5. Trauma
6. Cigarette smoking
7. Illicit drug use (especially cocaine)
8. Excessive alcohol consumption
9. Preterm premature rupture of the membranes
10. Rapid uterine decompression after delivery of the
first fetus in a twin gestation or rupture of mem-
branes with polyhydramnios
11. Uterine leiomyomas
C. Diagnosis of placental abruption
1. Abruption is characterized by vaginal bleeding,
abdominal pain, uterine tenderness, and uterine
contractions.
a. Vaginal bleeding is visible in 80%; bleeding is
concealed in 20%.
b. Pain is usually of sudden onset, constant, and
localized to the uterus and lower back.
c. Localized or generalized uterine tenderness and
increased uterine tone are found with severe
placental abruption.
d. An increase in uterine size may occur with pla-
cental abruption when the bleeding is con-
cealed. Concealed bleeding may be detected by
serial measurements of abdominal girth and
fundal height.
e. Amniotic fluid may be bloody.
f. Fetal monitoring may detect distress.
g. Placental abruption may cause preterm labor.
2. Uterine contractions by tocodynamometry is the
most sensitive indicator of abruption.
3. Laboratory findings include proteinuria and a
consumptive coagulopathy, characterized by de-
creased fibrinogen, prothrombin, factors V and VIII,
and platelets. Fibrin split products are elevated.
4. Ultrasonography has a sensitivity in detecting
placental abruption of only 15%.
D. Management of placental abruption
1. Mild placental abruption
a. If maternal stability and reassuring fetal surveil-
lance are assured and the fetus is immature,
close expectant observation with fetal monitoring
is justified.
b. Maternal hematologic parameters are monitored
and abnormalities corrected.
c. Tocolysis with magnesium sulfate is initiated if
the fetus is immature.
2. Moderate to severe placental abruption
a. Shock is aggressively managed.
b. Coagulopathy
(1) Blood is transfused to replace blood loss.
(2) Clotting factors may be replaced using
cryoprecipitate or fresh-frozen plasma. One
unit of fresh-frozen plasma increases
fibrinogen by 10 mg/dL. Cryoprecipitate con-
tains 250 mg fibrinogen/unit; 4 gm (15-20 U)
is an effective dose.
(3) Platelet transfusion is indicated if the platelet
count is <50,000/mcL. One unit of platelets
raises the platelet count 5000-10,000/mcL; 4
to 6 U is the smallest useful dose.
c. Oxygen should be administered and urine out-
put monitored with a Foley catheter.
d. Vaginal delivery is expedited in all but the mild-
est cases once the mother has been stabilized.
Amniotomy and oxytocin (Pitocin) augmentation
may be used. Cesarean section is indicated for
fetal distress, severe abruption, or failed trial of
labor.
III. Placenta previa occurs when any part of the placenta
implants in the lower uterine segment. It is associated
with a risk of serious maternal hemorrhage. Placenta
previa occurs in 1 in 200 pregnancies. Ninety% of pla-
centa previas diagnosed in the second trimester resolve
spontaneously.
A. Total placenta previa occurs when the internal cervi-
cal os is completely covered by placenta.
B. Partial placenta previa occurs when part of the cervi-
cal os is covered by placenta.
C. Marginal placenta previa occurs when the placental
edge is located within 2 cm of the cervical os.
D. Clinical evaluation
1. Placenta previa presents with a sudden onset of
painless vaginal bleeding in the second or third
trimester. The peak incidence occurs at 34 weeks.
The initial bleeding usually resolves spontaneously
and then recurs later in pregnancy.
2. One fourth of patients present with bleeding and
uterine contractions.
E. Ultrasonography is accurate in diagnosing placenta
previa.
F. Management of placenta previa
1. In a pregnancy >36 weeks with documented fetal
lung maturity, the neonate should be immediately
delivered by cesarean section.
2. Low vertical uterine incision is probably safer in
patients with an anterior placenta. Incisions
through the placenta should be avoided.
3. If severe hemorrhage jeopardizes the mother or
fetus, cesarean section is indicated regardless of
gestational age.
4. Expectant management is appropriate for imma-
ture fetuses if bleeding is not excessive, maternal
physical activity can be restricted, intercourse and
douching can be prohibited, and the hemoglobin
can be maintained at >10 mg/dL.
5. Rh immunoglobulin is administered to Rh-
negative-unsensitized patients.
6. Delivery is indicated once fetal lung maturity has
been documented.
7. Tocolysis with magnesium sulfate may be used for
immature fetuses.
IV. Cervical bleeding
A. Cytologic sampling is necessary.
B. Bleeding can be controlled with cauterization or pack-
ing.
C. Bacterial and viral cultures are sometimes diagnostic.
V. Cervical polyps
A. Bleeding is usually self-limited.
B. Trauma should be avoided.
C. Polypectomy may control bleeding and yield a
histologic diagnosis.
VI. Bloody show is a frequent benign cause of late third
trimester bleeding. It is characterized by blood-tinged
mucus associated with cervical change.
References: See page 208.

Preeclampsia
Preeclampsia is defined as the new onset of hypertension
and proteinuria after 20 weeks of gestation in a previously
normotensive woman. Preeclampsia is classified as mild or
severe. Eclampsia is defined as the development of seizures
in a woman with gestational hypertension or preeclampsia.

I. Clinical evaluation
A. Chronic hypertension is defined as systolic pressure
>140 mmHg, diastolic pressure >90 mmHg, or both,
that antedates pregnancy, is present before the 20th
week of pregnancy, or persists longer than 12 weeks
postpartum.
B. Preeclampsia superimposed upon chronic hyper-
tension occurs when a patient with preexisting hyper-
tension develops proteinuria after 20 weeks of gesta-
tion. Women with both preexisting hypertension and
proteinuria are considered preeclamptic if there is an
exacerbation of blood pressure to the severe range
(systolic >160 mmHg or diastolic >110 mmHg) in the
last half of pregnancy.
C. Gestational hypertension is defined as hypertension
without proteinuria (or other signs of preeclampsia)
developing in the latter part of pregnancy. Some
women with gestational hypertension will develop
preeclampsia later in the pregnancy.
II. Incidence. Hypertension occurs in 10 to 20% of pregnan-
cies.
A. Preeclampsia occurs in 5 to 8% of pregnancies. The
disease is mild in 75% of cases, and severe in 25%.
Ten% of preeclampsia occurs in pregnancies less
than 34 weeks of gestation.
B. Preexisting hypertension complicates about 3% of
pregnancies.
C. Gestational hypertension complicates about 6% of
pregnancies.
III. Risk factors for preeclampsia
A. Past obstetrical history of preeclampsia is a strong risk
factor for preeclampsia in a future pregnancy. In
women who had mild preeclampsia during the first
pregnancy, the incidence of preeclampsia in a second
pregnancy is 5 to 7%.
B. First pregnancy increases the risk for developing
preeclampsia (RR 2.91). A family history of
preeclampsia is associated with an increase in risk
(RR 2.90).
C. Pregestational diabetes increases risk of
preeclampsia (RR 3.56).
D. Multiple gestation increases the risk of preeclampsia;
for twin pregnancies the relative risk is 2.93.
E. Obesity increases the risk of preeclampsia.
F. Preexisting hypertension, renal disease, and collagen
vascular disease are risk factors.
G. The antiphospholipid syndrome has been associated
with preeclampsia, fetal loss, and maternal thrombo-
sis.
H. Advanced maternal age is an independent risk factor
for preeclampsia (maternal age >40 RR 1.96).
I. A prolonged interval between pregnancies appears to
increase the risk of developing preeclampsia.
J. Women who smoke cigarettes have a lower risk of
preeclampsia than nonsmokers.
IV. Clinical manifestations
A. Hypertension, proteinuria, and edema in pregnancy is
usually caused by preeclampsia, particularly in a
primigravida. These findings typically develop in the
latter part of the third trimester and progress until
delivery.
B. The occurrence of preeclampsia before 20 weeks of
gestation is unusual and may be suggestive of a mo-
lar pregnancy. The possibility of illicit drug use or with-
drawal or chromosomal aneuploidy in the fetus should
also be considered.
C. Pregnancy related hypertension is defined as a
systolic blood pressure >140 mmHg or diastolic blood
pressure >90 mmHg in a woman who was
normotensive prior to 20 weeks of gestation. Hyper-
tension is usually the earliest clinical finding of
preeclampsia. The blood pressure (BP) may rise in
the second trimester, but usually does not reach the
hypertensive range (>140/90 mmHg) until the third
trimester, often after the 37th week of gestation. In
some cases, however, preeclampsia develops sud-
denly in a previously normotensive woman or early in
pregnancy.
D. Proteinuria (>0.3 g protein in a 24-hour urine speci-
men or persistent 1+ on dipstick) must be present with
hypertension to diagnose preeclampsia.
E. Hyperuricemia and hypocalciuria also occur.
F. Edema. Most pregnant women have edema. How-
ever, sudden and rapid weight gain (eg, >5
pounds/week) and facial edema may occur in women
who develop preeclampsia.
G. Hematologic changes. The most common coagula-
tion abnormality in preeclampsia is thrombocytopenia.
Microangiopathic hemolysis may also occur and is
detected by examination of a blood smear for
schistocytes and helmet cells or elevation in the se-
rum lactate dehydrogenase concentration.
H. Liver. Glomerular and hepatic injury may be caused
by vasospasm and precipitation of fibrin in both or-
gans. The clinical manifestations of liver involvement
include right upper quadrant or epigastric pain, ele-
vated transaminases and subcapsular hemorrhage or
hepatic rupture, which may represent HELLP syn-
drome (Hemolysis, Elevated Liver function tests, Low
Platelets).
I. Central nervous system and eye manifestations of
preeclampsia include headache, blurred vision,
scotomata, and, rarely, cortical blindness. Seizures in
a preeclamptic woman signify a change in diagnosis
to eclampsia. One in 400 mildly preeclamptic and 2%
of severely preeclamptic women will develop
eclamptic seizures. Stroke is a rare complication of
severe preeclampsia/eclampsia.
J. Pulmonary edema. Elevated pulmonary vascular
hydrostatic pressure (PCWP) may produce pulmonary
edema in some women.
K. Fetus and placenta. Placental hypoperfusion may
cause fetal growth restriction and oligohydramnios.
Abruptio placenta is infrequent (<1%) with mild
preeclampsia, but occurs in 3% of severe disease.
L. Iatrogenic preterm delivery is a secondary result of
fetal or maternal complications.
V. Diagnosis
A. Diagnosis of preeclampsia is based upon hyperten-
sion and proteinuria developing after 20 weeks of
gestation in a woman who was previously
normotensive. Hypertension should be documented
on two occasions.
B. Screening for proteinuria. Testing is performed by
dipping a test strip into a urine specimen. Women with
proteinuria on dipstick should undergo quantitative
measurement of protein excretion (urine protein to
creatine ratio or 24-hour urine protein excretion).
 Diagnosis of Preeclampsia

Systolic blood pressure >140 mm Hg

or
Diastolic blood pressure > 90 mm Hg
AND
A random urine protein determination of 1+ on dipstick or
30 mg/dL or proteinuria of 0.3 g or greater in a 24-hour
urine specimen

Criteria for Gestational Hypertension

Systolic blood pressure >140 mm Hg

Diastolic blood pressure >90 mm Hg
AND no proteinuria
Developing AFTER the 20th week of gestation in women
known to be normotensive before pregnancy

Criteria for Severe Preeclampsia

New onset proteinuria hypertension and at least one

of the following:
Symptoms of central nervous system dysfunction:
Blurred vision, scotomata, altered mental status, severe
head-
ache
Symptoms of liver capsule distention: Right upper quad-
rant or epigastric pain
Hepatocellular injury: Serum transaminase concentration
at least twice normal
Severe blood pressure elevation: Systolic blood pressure
>160 mm Hg or diastolic >110 mm Hg on two occasions
at least six hours apart
Thrombocytopenia: <100,000 platelets per mm3
Proteinuria: Over 5 grams in 24 hours or 3+ or more on
two random samples four hours apart
Oliguria <500 mL in 24 hours
Intrauterine fetal growth restriction
Pulmonary edema or cyanosis
Cerebrovascular accident
Coagulopathy

VI. Laboratory evaluation

A. Hematocrit. Hemoconcentration supports the diag-
nosis of preeclampsia, but hemolysis can decrease
the hematocrit.
B. Platelet count. Thrombocytopenia is a criterion of
severe disease.
C. Quantification of protein excretion. Proteinuria is
defined as excretion of 300 mg or more in 24 hours
or at least 1+ protein on dipstick of two urine speci-
mens collected at least four hours apart; 3+ or
greater or 5 g or more per day is a criterion of severe
disease.
D. Serum creatinine concentration. An elevated or
rising level suggests severe disease.
E. Serum alanine and aspartate aminotransferase
concentrations (ALT and AST). Elevated or rising
levels suggest hepatic dysfunction indicative of se-
vere disease.
F. Lactate dehydrogenase (LDH). Microangiopathic
hemolysis is suggested by an elevated LDH level
and red cell fragmentation (schistocytes or helmet
cells) on peripheral blood smear. Microangiopathic
hemolysis is present in severe disease or HELLP
syndrome (Hemolysis, Elevated Liver function tests,
Low Platelets).
G. Serum uric acid is often elevated in preeclampsia.
H. Fetal well-being is evaluated by a nonstress test or
biophysical profile. The fetus is examined by ultra-
sound to evaluate growth and amniotic fluid volume.
I. Coagulation function tests. The prothrombin time,
activated partial thromboplastin time, and fibrinogen
concentration are usually normal if there is no
thrombocytopenia or liver dysfunction, and therefore
do not need to be monitored routinely.
VII. Management of preeclampsia. The definitive treatment
of preeclampsia is delivery to prevent development of
maternal or fetal complications from disease progression.
Patients at term are delivered, but preterm delivery is not
always in the best interests of the fetus. As a result, a
more conservative approach is often considered in se-
lected women remote from term. Maternal end-organ
dysfunction and nonreassuring tests of fetal well-being
may be indications for delivery at any gestational age.
A. Mild preeclampsia. At term, women are induced if
there are no contraindications to vaginal birth.
B. Women who are at least 37 weeks of gestation with
a favorable cervix (Bishop score >6) should be in-
duced. Delivery should be accomplished by 40
weeks of gestation for all preeclamptic women. Cervi-
cal ripening agents should be considered in women
with unfavorable cervices.
C. Women with mild disease remote from term can be
managed expectantly to enable further fetal growth
and maturation.
D. Inpatient versus outpatient care. Hospitalization is
useful for making initial assessments. After the initial
diagnostic evaluation, outpatient care is a cost-effec-
tive option for some women with mild preeclampsia.
1. Outpatients should be able to comply with frequent
maternal and fetal evaluations (every one to three
days) and have ready access to medical care.
Restricted activity is recommended. If signs or
symptoms of disease progression occur, hospital-
ization and delivery may be indicated.
2. Patients should be told to call if they develop se-
vere or persistent headache, visual changes, right
upper quadrant or epigastric pain, nausea or vomit-
ing, shortness of breath, or decreased urine output.
Decreased fetal movement, vaginal bleeding, ab-
dominal pain, rupture of membranes, or uterine
contractions should be reported immediately.

Fetal Assessment in Preeclampsia

Mild Daily fetal movement counting

preeclampsia Ultrasound examination for estima-
tion of fetal weight and amniotic fluid
determination at diagnosis. Repeat
in three weeks if the initial examina-
tion is normal, twice weekly if there is
evidence of fetal growth restriction or
oligohydramnios.
Nonstress test and/or biophysical
profile once or twice weekly. Testing
should be repeated immediately if
there is an abrupt change in mater-
nal condition.

Severe Daily nonstress testing and/or bio-

preeclampsia physical profile

E. Laboratory evaluation should include platelet count,

serum creatinine, serum ALT and AST. These tests
should be repeated once or twice weekly in women
with mild preeclampsia.
F. A rising hematocrit indicates hemoconcentration,
which suggests contraction of intravascular volume
and progression to more severe disease, while a
falling hematocrit may be a sign of hemolysis. An
elevated serum LDH concentration is also a sign of
hemolysis, and a marker of severe disease or HELLP
syndrome. Hemolysis can be confirmed by observa-
tion of schistocytes and helmet cells on a blood
smear.
G. Quantification of protein excretion can be per-
formed using a 24-hour collection or protein-to
creatinine ratio on a random specimen to determine
whether the threshold for severe preeclampsia (5 g/24
hours) has been reached.
H. Treatment of hypertension. Antihypertensive ther-
apy should be initiated at systolic pressures between
150 and 160 mm Hg and diastolic blood pressures
between 100 and 105 mm Hg. Target blood pres-
sures are 130 to 150 mm Hg systolic and 80 to 100
mm Hg diastolic.
1. Intravenous labetalol is recommended for acute
therapy because it is effective and generally safe in
pregnancy. Begin with 20 mg intravenously followed
at 10 minute intervals by doses of 20 to 80 mg up to
a maximum total cumulative dose of 300 mg. A
constant infusion of 1 to 2 mg/min can be used. The
oral dosage is 100 mg twice daily orally, maximum
dose 2400 mg/day.
I. Assessment of fetal well-being. Daily fetal movement
counts and twice weekly fetal nonstress testing with
assessment of amniotic fluid volume, or biophysical
profile are recommended.
J. Assessment of fetal growth. Early fetal growth re-
striction may be the first manifestation of preeclampsia
or a sign of severe preeclampsia. A sonographic esti-
mation of fetal weight should be performed to look for
growth restriction and oligohydramnios at the time of
diagnosis of preeclampsia and then repeated serially.
Doppler velocimetry is useful for assessing fetal status
if fetal growth restriction is present.
K. Antenatal corticosteroids (betamethasone) should
be administered to promote fetal lung maturity for
women less than 34 weeks of gestation since preterm
delivery is common (two doses of 12 mg given intra-
muscularly 24 hours apart).
L. Indications for delivery. Women with mild
preeclampsia should be delivered by 40 weeks of
gestation. Progression to eclampsia is also an indica-
tion for delivery.
1. Severe preeclampsia is generally regarded as an
indication for delivery, regardless of gestational age,
to minimize the risk of development of maternal and
fetal complications. Prolonged antepartum manage-
ment at a tertiary care setting or in consultation with
a maternal-fetal medicine specialist may be consid-
ered in selected women under 32 to 34 weeks of
gestation. However, women who develop severe
preeclampsia at or beyond 32 to 34 weeks of gesta-
tion should be delivered.
2. The decision to expedite delivery in the setting of
severe preeclampsia does not mandate immediate
cesarean birth. Cervical ripening agents may be
used prior to induction if the cervix is not favorable.

Indications for Delivery in Preeclampsia

Maternal indications Gestational age >38 weeks of ges-

tation
Platelet count <100,000 cells per
mm3
Deteriorating liver function
Progressive deterioration in renal
function
Abruptio placentae
Persistent severe headaches or vi-
sual changes
Persistent severe epigastric pain,
nausea, or vomiting

Fetal indications Severe fetal growth restriction

Nonreassuring results from fetal
testing
Oligohydramnios

VIII. Intrapartum monitoring. Close, continuous maternal-

fetal monitoring is indicated to identify worsening hyper-
tension, deteriorating maternal hepatic, renal,
cardiopulmonary, or hematologic function, and
uteroplacental insufficiency or abruptio placentae (often
manifested by nonreassuring fetal heart rate tracings
and/or vaginal bleeding).
A. A low platelet count may preclude neuraxial anesthe-
sia, which is associated with an increased risk of spi-
nal hematoma in this setting.
B. Invasive hemodynamic monitoring can be useful in
patients with severe cardiac disease, severe renal
disease, oliguria, refractory hypertension, or pulmo-
nary edema.
IX. Anticonvulsant therapy is started during labor and is
continued for 24 hours postpartum. Magnesium sulfate is
the drug of choice for the prevention of eclampsia.
A. Indications for treatment
1. Severe preeclampsia. Anticonvulsant therapy
should be administered to prevent a first seizure in
women with severe preeclampsia. Progression to
eclampsia is significantly lower with magnesium (0.3
versus 3.2%).
2. Mild preeclampsia. Anticonvulsant therapy is also
used for prevention of seizures in women with mild
preeclampsia.
3. Intrapartum magnesium sulfate seizure prophy-
laxis should be administered for preeclampsia, but
not for nonproteinuric gestational hypertension.
B. Magnesium is usually initiated at the onset of labor
or induction or prior to cesarean delivery. A loading
dose of 6 g is given intravenously over 15 to 20
minutes followed by 2 g per hour as a continuous
infusion.
1. Magnesium sulfate is excreted by the kidneys;
therefore, dosing should be adjusted in renal insuffi-
ciency (creatinine >1.0 mg/dL). Such women should
receive a standard loading dose, but a reduced
maintenance dose (1 g per hour or no maintenance
dose if creatinine is >2.5 mg/dL) and close monitor-
ing of serum magnesium level every six hours.
2. Magnesium sulfate is contraindicated in myasthenia
gravis since it can precipitate a severe myasthenic
crisis. Use of magnesium sulfate with calcium chan-
nel blockers may result in hypotension.
3. The maintenance phase is given only if a patellar
reflex is present (loss of reflexes being the first man-
ifestation of symptomatic hypermagnesemia), respi-
rations exceed 12 per minute, and the urine output
exceeds 100 mL per four hours. Following serum
magnesium levels is not required if clinical status is
closely monitored for signs of magnesium toxicity.
 4. Magnesium sulfate is usually continued for 24 hours
postpartum. In women who have only mild
preeclampsia, 12 hours may be adequate. In severe
preeclampsia or eclampsia, anticonvulsant drugs
are continued for 24 to 48 hours postpartum, when
the risk of recurrent seizures is low.
5. Complications. Rapid infusion of magnesium sul-
fate causes diaphoresis, flushing, and warmth. Nau-
sea, vomiting, headache, muscle weakness, visual
disturbances, and palpitations can also occur.
Dyspnea or chest pain may be symptoms of pulmo-
nary edema, a rare side effect of magnesium sulfate
administration.
6. Magnesium toxicity is related to serum concentra-
tion: loss of deep tendon reflexes occurs at 9.6 to
12.0 mg/dL, respiratory paralysis at 12.0 to 18.0
mg/dL, and cardiac arrest at 24 to 30 mg/dL. Cal-
cium gluconate (1 g intravenously over 5 to 10 min-
utes) should be administered only to counteract life-
threatening symptoms of magnesium toxicity (such
as cardiorespiratory compromise).
7. Hypocalcemia. Magnesium therapy also results in
a transient reduction of total and ionized serum
calcium concentration due to rapid suppression of
parathyroid hormone release. Rarely, the
hypocalcemia becomes symptomatic (myoclonus,
delirium, ECG abnormalities). Cessation of magne-
sium therapy will restore normal serum calcium
levels. However, calcium administration may be
required if symptoms are present (calcium
gluconate 1 g intravenously over 5 to 10 minutes).
X. Postpartum course. Hypertension and proteinuria due
to preeclampsia resolves postpartum, within a few days,
but sometimes taking a few weeks. Severe hypertension
should be treated; some patients will have to be dis-
charged on antihypertensive medications that can be
discontinued when blood pressure returns to normal.
Elevated blood pressures that remain 12 weeks
postpartum are probably not caused by preeclampsia
and may require long-term treatment.
References: See page 208.

Eclampsia
Eclampsia is defined as the occurrence of one or more
generalized convulsions and/or coma in the setting of
preeclampsia and in the absence of other neurologic condi-
tions. The manifestations appear anytime from the second
trimester to the puerperium. Seizures are only one of several
clinical manifestation of severe preeclampsia.
Preeclampsia/eclampsia is a common cause of maternal
death, along with thromboembolic disease and hemorrhage.

I. Incidence and epidemiology

A. An eclamptic seizure occurs in 0.5% of mildly
preeclamptic pregnancies and 2% of severe
preeclamptics. The incidence of eclampsia is 4 to 5
cases per 10,000 live births.
B. Eclampsia is more common in nonwhite, nulliparous
women from lower socioeconomic backgrounds. Peak
incidence is in the teenage years and low twenties,
but there is also an increased incidence in women
over 35 years of age. Risk factors are similar to those
for preclampsia.
C. Timing in pregnancy. Eclampsia prior to 20 weeks of
gestation is rare and should raise the possibility of an
underlying molar pregnancy or antiphospholipid syn-
drome.
D. One-half of all cases of eclampsia occur prior to term,
with more than one-fifth occurring before 31 weeks of
gestation. One-third of cases occur at term, develop-
ing intrapartum or within 48 hours of delivery. Late
postpartum eclampsia accounts for the remainder (13
to 16%).
II. Pathogenesis of seizures. Proposed etiologies of sei-
zures in women with eclampsia include (1) cerebral
vasospasm with local ischemia/infarction and cytotoxic
(intracellular) edema and (2) hypertensive
encephalopathy with hyperperfusion, vasogenic
(extracellular) edema, and endothelial damage.
III. Clinical manifestations and diagnosis
A. Maternal. Eclamptic seizures are almost always
self-limiting and usually last for 60-75 seconds (sel-
dom longer than 3 minutes). Persistent frontal or
occipital headache, blurred vision, photophobia, right
upper quadrant or epigastric pain, and altered mental
status may occur before the seizure.
B. The diagnosis of preeclampsia/eclampsia may not
be suspected prior to the development of seizures in
women with relative hypertension and no proteinuria.
However, 15 to 22% of eclamptic women have no
evidence of proteinuria prior to their seizure, 25 to
33% have no edema, and 16% have no hyperten-
sion.
C. Women with typical eclamptic seizures who do not
have focal neurologic deficits or prolonged coma do
not require either electroencephalographic or cere-
bral imaging studies. If cerebral imaging is per-
formed, MRI is the optimal study.
D. Fetal bradycardia lasting at least three to five min-
utes is a common finding during and immediately
after an eclamptic seizure, and does not necessitate
emergent cesarean delivery. Stabilizing the mother
by administering anticonvulsant drugs and oxygen
and treating severe hypertension can help the fetus
recover in-utero from the effects of maternal hypoxia,
hypercarbia, and uterine hyperstimulation.
E. Resolution of maternal seizure activity is associated
with compensatory tachycardia and loss of variability,
sometimes associated with transient fetal heart rate
decelerations which typically resolve within 20 to 30
minutes. However, if the fetal heart rate tracing re-
mains nonreassuring for more than 10 to 15 minutes
with no improvement despite maternal and fetal
resuscitative interventions, then occult abruption and
delivery should be considered.
IV. Differential diagnosis. Eclamptic seizures are clinically
and electro-encephalographically indistinguishable from
other generalized tonic-clonic seizures.
A. Differential diagnosis of seizures in pregnancy
1. Cerebrovascular accident (hemorrhage, arterial or
venous thrombosis).
2. Hypertensive disease (hypertensive
encephalopathy, pheochromocytoma).
3. Space-occupying lesions of the central nervous
system (brain tumor, abscess).
4. Metabolic disorders (hypoglycemia, uremia, inap-
propriate antidiuretic hormone secretion resulting
in water intoxication).
5. Infection (meningitis, encephalitis).
6. Thrombotic thrombocytopenic purpura or
thrombophilia.
7. Idiopathic epilepsy.
8. Use of methamphetamine, cocaine.
9. Cerebral vasculitis.
10. Reversible posterior leukoencephalopathy syn-
drome.
11. Postdural puncture syndrome.
V. Management
A. If the seizure is witnessed, maintenance of airway
patency and prevention of aspiration should be the
first responsibilities of management. The gravida
should be rolled onto her left side. Supplemental
oxygen (8 to 10 L/min) via a face mask is recom-
mended.
1. Maintenance of maternal vital functions to prevent
hypoxia
2. Control of convulsions and blood pressure
3. Prevention of recurrent seizures
4. Evaluation for prompt delivery
B. The definitive treatment of eclampsia is delivery,
irrespective of gestational age, to reduce the risk of
maternal morbidity and mortality.
C. Control of convulsions. The drug of choice is intra-
venous magnesium sulfate. A benzodiazepine is
another option. Phenytoin can also be used, but is
less effective in preventing recurrent seizures. Pre-
vention of recurrent convulsions is more important
than stopping the initial convulsion because it is usu-
ally of short duration.
1. Magnesium sulfate (6 g intravenously over 15
minutes) is administered to stop the convulsion.
An alternative dose/route is magnesium sulfate 5
g intramuscularly into each buttock. A diazepam
gel for rectal administration is available (0.2 mg/kg
). Magnesium sulfate is contraindicated in myas-
thenia gravis because it can cause myasthenic
crisis. Use of magnesium sulfate with calcium
channel blockers may cause hypotension.
2. Diazepam(0.1 to 0.3 mg/kg IV over 60 seconds,
max cumulative dose of 20 mg) achieves
anticonvulsant levels within one minute, and will
control seizures in >80% within five minutes.
Benzodiazepines should be avoided because of
profound depressant effects on the fetus and
mother.
D. Treatment of hypertension. Cerebrovascular acci-
dent accounts for 15-20% of deaths from eclampsia.
Antihypertensive therapy is recommended for dia-
stolic pressures of >105 to 110 mmHg and systolic
blood pressures of 160 mmHg.
1. Labetalol (Trandate). 10 or 20 mg intravenously
followed by doubling the dose at 10 minute inter-
vals up to 80 mg for a maximum total cumulative
dose of 220 to 230 mg. Goal is a systolic of 140-
155 mmHg and diastolic of 90-105 mmHg.
E. Prevention of subsequent seizures. Magnesium
sulfate is the drug of choice for prevention of recur-
rent eclamptic seizures.
1. Maintenance magnesium doseafter the initial 6
g loading dose is 2 to 3 g/hour intravenous infu-
sion. The maintenance phase is given only if a
patellar reflex is present, respirations are >12 per
minute, and urine output >100 mL in four hours.
2. Recurrent convulsions occurring in patients on
maintenance magnesium sulfate therapy can be
treated with an additional bolus of 2 grams of
magnesium sulfate over 15 to 20 minutes. If two
boluses of magnesium sulfate do not control sei-
zures, lorazepam (Ativan) 0.02 to 0.03 mg/kg
intravenously is administered. If seizures continue,
additional doses of lorazepam (up to a cumulative
dose of 0.1 mg/kg) should be infused at a max 2
mg/minute. Other options include amobarbital
(250 mg IV over 3 to 5 minutes), phenytoin or
paralysis with intubation and mechanical ventila-
tion.
F. Delivery. Eclampsia is usually an absolute contrain-
dication to expectant management. The definitive
treatment for eclampsia is delivery.
1. Cesarean delivery is a reasonable option for
women with severe preeclampsia/eclampsia re-
mote from term (eg, <28 to 32 weeks gestation)
with an unfavorable cervix and not in labor.
2. Cervical ripening agents can be used to improve
the Bishop score; however, long inductions should
be avoided (eg, 24 hours).
G. Postpartum course. Seizures due to eclampsia
always resolve postpartum, generally within a few
hours to days. Anticonvulsant drugs are continued for
24 to 48 hours postpartum.
References: See page 208.

Herpes Simplex Virus Infections in

Pregnancy
Herpes simplex virus (HSV) is a major source of morbidity
and mortality for newborns infected with HSV. HSV-2 is
primarily responsible for genital HSV disease. Spread is
principally through sexual contact. The incidence is 22%. The
majority of cases are asymptomatic or symptoms are unrec-
ognized. HSV-1 infection generally involves the mucosal
surfaces of the mouth, pharynx, lips and eyes, but the virus
can also be recovered from genital lesions.

I. Clinical presentation
A. Primary genital episode genital HSV is character-
ized by multiple painful vesicles in clusters. They may
be associated with pruritus, dysuria, vaginal dis-
charge, and tender regional adenopathy. Fever, mal-
aise, and myalgia often occur one to two days prior to
the appearance of lesions. The lesions may last four
to five days prior to crusting. The skin will
reepithelialize in about 10 days. Viral shedding may
last for 10 to 12 days after reepithelialization.
B. Nonprimary first-episode genital HSV refers to
patients with preexisting antibodies to one of the two
types of virus who acquire the other virus and develop
genital lesions. Nonprimary disease is less severe
with fewer systemic symptoms, and less local pain.
C. Recurrent HSV episodes are characterized by local
pain or paresthesia followed by vesicular lesions.
Lesions are generally fewer in number and often uni-
lateral but may be painful.
II. Diagnosis
A. PCR to detect HSV DNA from lesions or genital se-
cretions is recommended for diagnosis. The gold
standard for diagnosis of acute HSV infection is viral
culture. Although the highest yield is from vesicular
fluid of skin lesions, cultures may be obtained from the
eyes, mouth, cerebral spinal fluid, rectum, urine, and
blood.

Clinical Designation of Genital Herpes Simplex Virus

Infection

Primary genital HSV infection

Antibodies to both HSV-1 and HSV-2 are absent at
the time the patient acquires genital HSV due to
HSV-1 or HSV-2

Nonprimary first episode genital HSV infection

Acquisition of genital HSV-1 with pre-existing anti-
bodies to HSV-2 or acquisition of genital HSV-2
with pre-existed antibodies rto HSV-1
 Recurrent genital HSV infection
Reactivation of genital HSV in which the HSV type
recovered from the lesion is the same type as anti-
bodies in the serum

III. Maternal treatment

A. Primary infection. Acyclovir therapy (200 mg PO five
times per day or 400 mg PO TID for 7 to 14 days) is
recommended. Acyclovir is safe in pregnancy.
Acyclovir should be administered to pregnant women
experiencing a first episode of HSV during pregnancy
to reduce the duration of active lesions. Suppressive
therapy (400 mg PO BID) for the remainder of preg-
nancy should also be considered.
B. Recurrent infection. Women with one or more HSV
recurrence during pregnancy benefit from suppression
given at 36 weeks of gestation through delivery.
C. Cesarean delivery should be offered to women who
have active lesions or symptoms of vulvar pain or
burning at the time of delivery in those with a history of
genital herpes. However, delivery by cesarean birth
does not prevent all infections. Approximately 20 to
30% of HSV-infected infants are born by cesarean.
Prophylactic cesarean delivery is not recommended
for women with recurrent HSV and no evidence of
active lesions at the time of delivery. Lesions which
have crusted fully are considered healed and not
active.
D. Prevention
1. Nongenital invasive procedures (eg, amniocente-
sis) should be delayed if there is evidence of sys-
temic disease. Use of fetal scalp electrodes should
be avoided among women who are known to have
recurrent HSV, and who are in labor.
2. Mothers with active lesions should cover their le-
sions, and hands should be washed before touch-
ing the baby. Breastfeeding is not contraindicated
as long as there are no breast lesions.
References: See page 208.

Dystocia and Augmentation of Labor

I. Normal labor
A. First stage of labor
1. The first stage of labor consists of the period from
the onset of labor until complete cervical dilation (10
cm). This stage is divided into the latent phase and
the active phase.
2. Latent phase
a. During the latent phase, uterine contractions are
infrequent and irregular and result in only modest
discomfort. They result in gradual effacement and
dilation of the cervix.
b. A prolonged latent phase is one that exceeds 20
hours in the nullipara or one that exceeds 14
hours in the multipara.
3. Active phase
a. The active phase of labor occurs when the cervix
reaches 3-4 cm of dilatation.
b. The active phase of labor is characterized by an
increased rate of cervical dilation and by descent
of the presenting fetal part.
B. Second stage of labor
1. The second stage of labor consists of the period
from complete cervical dilation (10 cm) until delivery
of the infant. This stage is usually brief, averaging 20
minutes for parous women and 50 minutes for
nulliparous women.
2. The duration of the second stage of labor is unre-
lated to perinatal outcome in the absence of a
nonreassuring fetal heart rate pattern as long as
progress occurs.
II. Abnormal labor
A. Dystocia is defined as difficult labor or childbirth result-
ing from abnormalities of the cervix and uterus, the
fetus, the maternal pelvis, or a combination of these
factors.
B. Cephalopelvic disproportion is a disparity between
the size of the maternal pelvis and the fetal head that
precludes vaginal delivery. This condition can rarely be
diagnosed in advance.
C. Slower-than-normal (protraction disorders) or com-
plete cessation of progress (arrest disorder) are
disorders that can be diagnosed only after the parturient
has entered the active phase of labor.
III. Assessment of labor abnormalities
A. Labor abnormalities caused by inadequate uterine
contractility (powers). The minimal uterine contractile
pattern of women in spontaneous labor consists of 3 to
5 contractions in a 10-minute period.
B. Labor abnormalities caused by fetal characteristics
(passenger)
1. Assessment of the fetus consists of estimating fetal
weight and position. Estimations of fetal size, even
those obtained by ultrasonography, are frequently
inaccurate.
2. In the first stage of labor, the diagnosis of dystocia
can not be made unless the active phase of labor
and adequate uterine contractile forces have been
present.
3. Fetal anomalies such as hydrocephaly,
encephalocele, and soft tissue tumors may obstruct
labor. Fetal imaging should be considered when
malpresentation or anomalies are suspected based
on vaginal or abdominal examination or when the
presenting fetal part is persistently high.
C. Labor abnormalities due to the pelvic passage
(passage)
1. Inefficient uterine action should be corrected before
attributing dystocia to a pelvic problem.
2. The bony pelvis is very rarely the factor that limits
vaginal delivery of a fetus in cephalic presentation.
Radiographic pelvimetry is of limited value in manag-
ing most cephalic presentations.
3. Clinical pelvimetry can only be useful to qualitatively
identify the general architectural features of the pel-
vis.
IV. Augmentation of labor
A. Uterine hypocontractility should be augmented only
after both the maternal pelvis and fetal presentation
have been assessed.
B. Contraindications to augmentation include placenta or
vasa previa, umbilical cord prolapse, prior classical
uterine incision, pelvic structural deformities, and inva-
sive cervical cancer.
C. Oxytocin (Pitocin)
1. The goal of oxytocin administration is to stimulate
uterine activity that is sufficient to produce cervical
change and fetal descent while avoiding uterine
hyperstimulation and fetal compromise.
2. Minimally effective uterine activity is 3 contrac-
tions per 10 minutes averaging >25 mm Hg above
baseline. A maximum of 5 contractions in a 10-min-
ute period with resultant cervical dilatation is consid-
ered adequate.
3. Hyperstimulation is characterized by more than five
contractions in 10 minutes, contractions lasting 2
minutes or more, or contractions of normal duration
occurring within 1 minute of each other.
4. Oxytocin is administered when a patient is progress-
ing slowly through the latent phase of labor or has a
protraction or an arrest disorder of labor, or when a
hypotonic uterine contraction pattern is identified.
5. A pelvic examination should be performed before
initiation of oxytocin infusion.
6. Oxytocin is usually diluted 10 units in 1 liter of normal
saline IVPB.

Labor Stimulation with Oxytocin (Pitocin)

Starting Incremental Dosage Maximum

Dose Increase Interval Dose
(mU/min) (mU/min) (min) (mU/min)

6 6 15 40

7. Management of oxytocin-induced
hyperstimulation
a. The most common adverse effect of
hyperstimulation is fetal heart rate deceleration
associated with uterine hyperstimulation. Stop-
ping or decreasing the dose of oxytocin may
correct the abnormal pattern.
b. Additional measures may include changing the
patient to the lateral decubitus position and
administering oxygen or more intravenous fluid.

c. If oxytocin-induced uterine hyperstimulation

does not respond to conservative measures,
intravenous terbutaline (0.125-0.25 mg) or
magnesium sulfate (2-6 g in 10-20% dilution)
may be used to stop uterine contractions.
References: See page 208.

Fetal Macrosomia
Excessive birth weight is associated with an increased risk of
maternal and neonatal injury. Macrosomia is defined as a
fetus with an estimated weight of more than 4,500 grams,
regardless of gestational age.
I. Diagnosis of macrosomia
A. Clinical estimates of fetal weight based on Leopold's
maneuvers or fundal height measurements are often
inaccurate.
B. Diagnosis of macrosomia requires ultrasound evalua-
tion; however, estimation of fetal weight based on ultra-
sound is associated with a large margin of error.
C. Maternal weight, height, previous obstetric history,
fundal height, and the presence of gestational diabetes
should be evaluated.
II. Factors influencing fetal weight
A. Gestational age. Post-term pregnancy is a risk factor
for macrosomia. At 42 weeks and beyond, 2.5% of
fetuses weigh more than 4,500 g. Ten to twenty% of
macrosomic infants are post-term fetuses.
B. Maternal weight. Heavy women have a greater risk of
giving birth to excessively large infants. Fifteen to 35%
of women who deliver macrosomic fetuses weigh 90 kg
or more.
C. Multiparity. Macrosomic infants are 2-3 times more
likely to be born to parous women.
D. Macrosomia in a prior infant. The risk of delivering an
infant weighing more than 4,500 g is increased if a prior
infant weighed more than 4,000 g.
E. Maternal diabetes
1. Maternal diabetes increases the risk of fetal
macrosomia and shoulder dystocia.
2. Cesarean delivery is indicated when the estimated
fetal weight exceeds 4,500 g.
III. Morbidity and mortality
A. Abnormalities of labor. Macrosomic fetuses have a
higher incidence of labor abnormalities and instrumen-
tal deliveries.
B. Maternal morbidity. Macrosomic fetuses have a two-
to threefold increased rate of cesarean delivery.
C. Birth injury
1. The incidence of birth injuries occurring during deliv-
ery of a macrosomic infant is much greater with
vaginal than with cesarean birth. The most common
injury is brachial plexus palsy, often caused by
shoulder dystocia.
2. The incidence of shoulder dystocia in infants weigh-
ing more than 4,500 g is 8-20%. Macrosomic infants
also may sustain fractures of the clavicle or hu-
merus.
IV. Management of delivery
A. If the estimated fetal weight is >4500 gm in the
nondiabetic or >4000 gm in the diabetic patient, deliv-
ery by cesarean section is indicated.
B. Management of shoulder dystocia
1. If a shoulder dystocia occurs, an assistant should
provide suprapubic pressure to dislodge the im-
pacted anterior fetal shoulder from the symphysis.
McRoberts maneuver (extreme hip flexion) should
be done simultaneously.
2. If the shoulder remains impacted anteriorly, an am-
ple episiotomy should be cut and the posterior arm
delivered.
3. In almost all instances, one or both of these proce-
dures will result in successful delivery. The Zavanelli
maneuver consists of replacement of the fetal lead
into the vaginal canal and delivery by emergency
cesarean section.
4. Fundal pressure is not recommended because it
often results in further impaction of the shoulder
against the symphysis.
References: See page 208.

Shoulder Dystocia
Shoulder dystocia, defined as failure of the shoulders to
deliver following the head, is an obstetric emergency. The
incidence varies from 0.6% to 1.4% of all vaginal deliveries.
Up to 30% of shoulder dystocias can result in brachial plexus
injury; many fewer sustain serious asphyxia or death. Most
commonly, size discrepancy secondary to fetal macrosomia
is associated with difficult shoulder delivery. Causal factors of
macrosomia include maternal diabetes, postdates gestation,
and obesity. The fetus of the diabetic gravida may also have
disproportionately large shoulders and body size compared
with the head.
I. Prediction
A. The diagnosis of shoulder dystocia is made after deliv-
ery of the head. The “turtle” sign is the retraction of the
chin against the perineum or retraction of the head into
the birth canal. This sign demonstrates that the shoul-
der girdle is resisting entry into the pelvic inlet, and
possibly impaction of the anterior shoulder.
B. Macrosomia has the strongest association. ACOG
defines macrosomia as an estimated fetal weight
(EFW) >4500 g.
C. Risk factors for macrosomia include maternal birth
weight, prior macrosomia, preexisting diabetes, obe-
 sity, multiparity, advanced maternal age, and a prior
shoulder dystocia. The recurrence rate has been re-
ported to be 13.8%, nearly seven times the primary
rate. Shoulder dystocia occurs in 5.1% of obese
women. In the antepartum period, risk factors include
gestational diabetes, excessive weight gain, short
stature, macrosomia, and postterm pregnancy.
Intrapartum factors include prolonged second stage of
labor, abnormal first stage, arrest disorders, and instru-
mental (especially midforceps) delivery. Many shoulder
dystocias will occur in the absence of any risk factors.
II. Management
A. Shoulder dystocia is a medical and possibly surgical
emergency. Two assistants should be called for if not
already present, as well as an anesthesiologist and
pediatrician. A generous episiotomy should be cut. The
following sequence is suggested:
1. McRoberts maneuver: The legs are removed from
the lithotomy position and flexed at the hips, with
flexion of the knees against the abdomen. Two
assistants are required. This maneuver may be
performed prophylactically in anticipation of a diffi-
cult delivery.
2. Suprapubic pressure: An assistant is requested to
apply pressure downward, above the symphysis
pubis. This can be done in a lateral direction to help
dislodge the anterior shoulder from behind the pu-
bic symphysis. It can also be performed in anticipa-
tion of a difficult delivery. Fundal pressure may in-
crease the likelihood of uterine rupture and is con-
traindicated.
3. Rotational maneuvers: The Woods' corkscrew
maneuver consists of placing two fingers against
the anterior aspect of the posterior shoulder. Gentle
upward rotational pressure is applied so that the
posterior shoulder girdle rotates anteriorly, allowing
it to be delivered first. The Rubin maneuver is the
reverse of Woods's maneuver. Two fingers are
placed against the posterior aspect of the posterior
(or anterior) shoulder and forward pressure applied.
This results in adduction of the shoulders and dis-
placement of the anterior shoulder from behind the
symphysis pubis.
4. Posterior arm release: The operator places a
hand into the posterior vagina along the infant's
back. The posterior arm is identified and followed to
the elbow. The elbow is then swept across the
chest, keeping the elbow flexed. The fetal forearm
or hand is then grasped and the posterior arm deliv-
ered, followed by the anterior shoulder. If the fetus
still remains undelivered, vaginal delivery should be
abandoned and the Zavanelli maneuver performed
followed by cesarean delivery.
5. Zavanelli maneuver: The fetal head is replaced
into the womb. Tocolysis is recommended to pro-
duce uterine relaxation. The maneuver consists of
rotation of the head to occiput anterior. The head is
then flexed and pushed back into the vagina, fol-
lowed abdominal delivery. Immediate preparations
should be made for cesarean delivery.
6. If cephalic replacement fails, an emergency
symphysiotomy should be performed. The urethra
should be laterally displaced to minimize the risk of
lower urinary tract injury.
B. The McRoberts maneuver alone will successfully alle-
viate the shoulder dystocia in 42% to 79% of cases.
For those requiring additional maneuvers, vaginal
delivery can be expected in more than 90%. Finally,
favorable results have been reported for the Zavanelli
maneuver in up to 90%.
References: See page 208.

Postdates Pregnancy
A term gestation is defined as one completed in 38 to 42
weeks. Pregnancy is considered prolonged or postdates
when it exceeds 294 days or 42 weeks from the first day of
the last menstrual period (LMP). About 10% of those preg-
nancies are postdates. The incidence of patients reaching
the 42nd week is 3-12%.

I. Morbidity and mortality

A. The rate of maternal, fetal, and neonatal complications
increases with gestational age. The cesarean delivery
rate more than doubles when passing the 42nd week
compared with 40 weeks because of cephalopelvic
disproportion resulting from larger infants and by fetal
intolerance of labor.
B. Neonatal complications from postdates pregnancies
include placental insufficiency, birth trauma from
macrosomia, meconium aspiration syndrome, and
oligohydramnios.
II. Diagnosis
A. The accurate diagnosis of postdates pregnancy can be
made only by proper dating. The estimated date of
confinement (EDC) is most accurately determined
early in pregnancy. An EDC can be calculated by
subtracting 3 months from the first day of the last men-
ses and adding 7 days (Naegele's rule). Other clinical
parameters that should be consistent with the EDC
include maternal perception of fetal movements (quick-
ening) at about 16 to 20 weeks; first auscultation of
fetal heart tones with Doppler ultrasound by 12 weeks;
uterine size at early examination (first trimester) consis-
tent with dates; and, at 20 weeks, a fundal height 20
cm above the symphysis pubis or at the umbilicus.

Clinical Estimates of Gestational Age

Parameter Gestational age (weeks)

Positive urine hCG 5

Fetal heart tones by Doppler 11 to 12

Quickening
Primigravida 20
Multigravida 16

Fundal height at umbilicus 20

B. In patients without reliable clinical data, ultrasound is

beneficial. Ultrasonography is most accurate in early
gestation. The crown-rump length becomes less
accurate after 12 weeks in determining gestational
age because the fetus begins to curve.
III. Management of the postdates pregnancy
A. A postdates patient with a favorable cervix should
receive induction of labor. Only 8.2% of pregnancies
at 42 weeks have a ripe cervix (Bishop score >6).
Induction at 41 weeks with cervical ripening lowers
the cesarean delivery rate.
B. Placement of a balloon catheter immediately fol-
lowed by vaginal or intracervical prostaglandin E2
administration is recommended. Oxytocin, if required,
can be started six hours after the last prostaglandin
dose.
C. Stripping of membranes, starting at 38 weeks and
repeated weekly may be an effective method of in-
ducing labor in post-term women with a favorable
cervix. Stripping of membranes is performed by plac-
ing a finger in the cervical os and circling 3 times in
the plane between the fetal head and cervix.
D. Expectant management with antenatal surveil-
lance
1. Begin testing near the end of the 41st week of
pregnancy. Antepartum testing consists of the
nonstress test (NST) combined with the amniotic
fluid index (AFI) twice weekly. The false-negative
rate is 6.1/1000 (stillbirth within 1 week of a reas-
suring test) with twice weekly NSTs.
2. The AFI involves measuring the deepest vertical
fluid pocket in each uterine quadrant and summing
the four together. Less than 5 cm is considered
oligohydramnios, 5 to 8 cm borderline, and >8 cm
normal.
E. Fetal movement counting (kick counts). Fetal
movement has been correlated with fetal health. It
consist of having the mother lie on her side and count
fetal movements. Perception of 10 distinct move-
ments in a period of up to 2 hours is considered reas-
suring. After 10 movements have been perceived, the
count may be discontinued.
F. Delivery is indicated if the amniotic fluid index is <5
cm, a nonreactive non-stress test is identified, or if
decelerations are identified on the nonstress test.
G. Intrapartum management
1. Meconium staining is more common in postdates
pregnancies. If oligohydramnios is present,
amnioinfusion dilutes meconium and decreases
the number of infants with meconium below the
vocal cords. Instillation of normal saline through an
intrauterine pressure catheter may reduce variable
decelerations.
2. Macrosomia should be suspected in all postdates
gestations. Fetal weight should be estimated prior
to labor in all postdates pregnancies.
Ultrasonographic weight predictions generally fall
within 20% of the actual birth weight.
3. Management of suspected macrosomia. The
pediatrician and anesthesiologist should be notified
so that they can prepare for delivery. Cesarean
delivery should be considered in patients with an
estimated fetal weight >4500 g and a marginal
pelvis, or someone with a previous difficult vaginal
delivery with a similarly sized or larger infant.
4. Intrapartum asphyxia is also more common in the
postdates pregnancy. Therefore, close observation
of the fetal heart rate tracing is necessary during
labor. Variable decelerations representing cord
compression are frequently seen in postdates
pregnancies
5. Cord compression can be treated with
amnioinfusion, which can reduce variable deceler-
ations. Late decelerations are more direct evi-
dence of fetal hypoxia. If intermittent, late decelera-
tions are managed conservatively with positioning
and oxygen. If persistent late decelerations are
associated with decreased variability or an ele-
vated baseline fetal heart rate, immediate evalua-
tion or delivery is indicated. This additional evalua-
tion can include observation for fetal heart acceler-
ation following fetal scalp or acoustic stimulation, or
a fetal scalp pH.
References: See page 208.

Induction of Labor
Induction of labor refers to stimulation of uterine contractions
prior to the onset of spontaneous labor. Between 1990 and
1998, the rate of labor induction doubled from 10 to 20%.
I. Indications for labor induction:
A. Preeclampsia/eclampsia, and other hypertensive
diseases
B. Maternal diabetes mellitus
C. Prelabor rupture of membranes
D. Chorioamnionitis
E. Intrauterine fetal growth restriction (IUGR)
F. Isoimmunization
G. In-utero fetal demise
H. Postterm pregnancy
II. Absolute contraindications to labor induction:
A. Prior classical uterine incision
B. Active genital herpes infection
C. Placenta or vasa previa
D. Umbilical cord prolapse
E. Fetal malpresentation, such as transverse lie
II. Requirements for induction
A. Prior to undertaking labor induction, assessments of
gestational age, fetal size and presentation, clinical
pelvimetry, and cervical examination should be per-
formed. Fetal maturity should be evaluated, and am-
niocentesis for fetal lung maturity may be needed prior
to induction.
B. Clinical criteria that confirm term gestation:
1. Fetal heart tones documented for 30 weeks by
Doppler.
2. Thirty-six weeks have elapsed since a serum or
urine human chorionic gonadotropin (hCG) preg-
nancy test was positive.
3. Ultrasound measurement of the crown-rump length
at 6 to 11 weeks of gestation or biparietal diame-
ter/femur length at 12 to 20 weeks of gestation
support a clinically determined gestational age
equal to or >39 weeks.
C. Assessment of cervical ripeness
1. A cervical examination should be performed before
initiating attempts at labor induction.
2. The modified Bishop scoring system is most com-
monly used to assess the cervix. A score is calcu-
lated based upon the station of the presenting part
and cervical dilatation, effacement, consistency,
and position.

Modified Bishop Scoring System

0 1 2 3

Dilation, cm Closed 1-2 3-4 5-6

Effacement, 0-30 40-50 60-70 >80

percent

Station* -3 -2 -1, 0 +1, +2

Cervical Firm Medium Soft

consistency

Position of Posterior Midposi- Anterior

the cervix tion

* Based on a -3 to +3 scale.
 3. The likelihood of a vaginal delivery after labor
induction is similar to that after spontaneous
onset of labor if the Bishop score is >8.
III. Induction of labor with oxytocin
A. The uterine response to exogenous oxytocin admin-
istration is periodic uterine contractions.
B. Oxytocin regimen (Pitocin)
1. Oxytocin is given intravenously. Oxytocin is
diluted by placing 10 units in 1000 mL of normal
saline, yielding an oxytocin concentration of 10
mU/mL. Begin at 6 mU/min and increase by 6
mU/min every 15 minutes.
2. Active management of labor regimens use a
high-dose oxytocin infusion with short incremen-
tal time intervals.

High Dose Oxytocin Regimen

Begin oxytocin 6 mU per minute intravenously

Increase dose by 6 mU per minute every 15 minutes
Maximum dose: 40 mU per minute
Maximum total dose administered-during-labor: 10 U
Maximum duration of administration: six hours

3. The dose of maximum oxytocin is usually 40

mU/min. The dose is typically increased until
contractions occur at two to three minute intervals.
IV. Cervical ripening agents
A. A ripening process should be considered prior to use
of oxytocin use when the cervix is unfavorable.
B. Mechanical methods
1. Membrane stripping is a widely utilized technique,
which causes release of either prostaglandin F2-
alpha from the decidua and adjacent membranes
or prostaglandin E2 from the cervix. Weekly mem-
brane stripping beginning at 38 weeks of gestation
results in delivery within a shorter period of time
(8.6 versus 15 days).
2. Amniotomy is an effective method of labor induc-
tion when performed in women with partially dilated
and effaced cervices. Caution should be exercised
to ensure that the fetal vertex is well-applied to the
cervix and the umbilical cord or other fetal part is
not presenting.
3. Foley catheter. An uninflated Foley catheter can
be passed through an undilated cervix and then
inflated. This technique is as effective as prosta-
glandin E2 gel. The use of extra-amniotic saline
infusion with a balloon catheter or a double balloon
catheter (Atad ripener) also appears to be effective
for cervical ripening.
C. Prostaglandins
1. Local administration of prostaglandins to the vagina
or the endocervix is the route of choice because of
fewer side effects and acceptable clinical response.
Uncommon side effects include fever, chills, vomit-
ing, and diarrhea.
2. Prepidil contains 0.5 mg of dinoprostone in 2.5 mL
of gel for intracervical administration. The dose can
be repeated in 6 to 12 hours if there is inadequate
cervical change and minimal uterine activity follow-
ing the first dose. The maximum cumulative dose is
1.5 mg (ie, 3 doses) within a 24-hour period. The
time interval between the final dose and initiation of
oxytocin should be 6 to 12 hours because of the
potential for uterine hyperstimulation with concur-
rent oxytocin and prostaglandin administration.
3. Cervidil is a vaginal insert containing 10 mg of
dinoprostone in a timed-release formulation. The
vaginal insert administers the medication at 0.3
mg/h and should be left in place for 12 hours.
Oxytocin may be initiated 30 to 60 minutes after
removal of the insert.
4. An advantage of the vaginal insert over the gel
formulation is that the insert can be removed in
cases of uterine hyperstimulation or abnormalities
of the fetal heart rate tracing.
V. Complications of labor induction
A. Hyperstimulation and tachysystole may occur with
use of prostaglandin compounds or oxytocin.
Hyperstimulation is defined as uterine contractions
lasting at least two minutes or five or more uterine
contractions in 10 minutes. Tachysystole is defined as
six or more contractions in 20 minutes.
B. Prostaglandin E2 (PGE2) preparations have up to a
5% rate of uterine hyperstimulation. Fetal heart rate
abnormalities can occur, but usually resolve upon
removal of the drug. Rarely hyperstimulation or
tachysystole can cause uterine rupture. Removing the
PGE2 vaginal insert will usually help reverse the
effects of the hyperstimulation and tachysystole.
Cervical and vaginal lavage after local application of
prostaglandin compounds is not helpful.
C. If oxytocin is being infused, it should be discontinued
to achieve a reassuring fetal heart rate pattern. Placing
the woman in the left lateral position, administering
oxygen, and increasing intravenous fluids may also be
of benefit. Terbutaline 0.25 mg subcutaneously (a
tocolytic) may be given.
References: See page 208.

Postpartum Hemorrhage
Obstetric hemorrhage remains a leading causes of mater-
nal mortality. Postpartum hemorrhage is defined as the loss
of more than 500 mL of blood following delivery. However,
the average blood loss in an uncomplicated vaginal delivery
is about 500 mL, with 5% losing more than 1,000 mL.

I. Clinical evaluation of postpartum hemorrhage

A. Uterine atony is the most common cause of
postpartum hemorrhage. Conditions associated with
uterine atony include an overdistended uterus (eg,
polyhydramnios, multiple gestation), rapid or pro-
longed labor, macrosomia, high parity, and
chorioamnionitis.
B. Conditions associated with bleeding from trauma
include forceps delivery, macrosomia, precipitous
labor and delivery, and episiotomy.
C. Conditions associated with bleeding from
coagulopathy and thrombocytopenia include
abruptio placentae, amniotic fluid embolism,
preeclampsia, coagulation disorders, autoimmune
thrombocytopenia, and anticoagulants.
D. Uterine rupture is associated with previous uterine
surgery, internal podalic version, breech extraction,
multiple gestation, and abnormal fetal presentation.
High parity is a risk factor for both uterine atony and
rupture.
E. Uterine inversion is detected by abdominal vaginal
examination, which will reveal a uterus with an unusual
shape after delivery.
II. Management of postpartum hemorrhage
A. Following delivery of the placenta, the uterus should
be palpated to determine whether atony is present. If
atony is present, vigorous fundal massage should be
administered. If bleeding continues despite uterine
massage, it can often be controlled with bimanual
uterine compression.
B. Genital tract lacerations should be suspected in
patients who have a firm uterus, but who continue to
bleed. The cervix and vagina should be inspected to
rule out lacerations. If no laceration is found but bleed-
ing is still profuse, the uterus should be manually ex-
amined to exclude rupture.
C. The placenta and uterus should be examined for
retained placental fragments. Placenta accreta is
usually manifest by failure of spontaneous placental
separation.
D. Bleeding from non-genital areas (venous puncture
sites) suggests coagulopathy. Laboratory tests that
confirm coagulopathy include INR, partial
thromboplastin time, platelet count, fibrinogen, fibrin
split products, and a clot retraction test.
E. Medical management of postpartum hemorrhage
1. Oxytocin (Pitocin) is usually given routinely imme-
diately after delivery to stimulate uterine firmness
and diminish blood loss. 20 units of oxytocin in
1,000 mL of normal saline or Ringer's lactate is
administered at 100 drops/minute. Oxytocin should
not be given as a rapid bolus injection because of
the potential for circulatory collapse.
2. Methylergonovine (Methergine) 0.2 mg can be
given IM if uterine massage and oxytocin are not
effective in correcting uterine atony and provided
there is no hypertension.
3. 15-methyl prostaglandin F2-alpha (Hemabate),
one ampule (0.25 mg), can be given IM, with repeat
injections every 20min, up to 4 doses can be given
if hypertension is present; it is contraindicated in
asthma.

Treatment of Postpartum Hemorrhage Secondary

to Uterine Atony

Drug Protocol

Oxytocin 20 U in 1,000 mL of lactated

Ringer's as IV infusion

Methylergonovine 0.2 mg IM
(Methergine)

Prostaglandin (15 methyl 0.25 mg as IM every 15-60 min-

PGF2-alpha [Hemabate, utes as necessary
Prostin/15M])

F. Volume replacement
1. Patients with postpartum hemorrhage that is re-
fractory to medical therapy require a second large-
bore IV catheter. If the patient has had a major
blood group determination and has a negative
indirect Coombs test, type-specific blood may be
given without waiting for a complete cross-match.
Lactated Ringer's solution or normal saline is gen-
erously infused until blood can be replaced. Re-
placement consists of 3 mL of crystalloid solution
per 1 mL of blood lost.
2. A Foley catheter is placed, and urine output is
maintained at >30 mL/h.
G. Surgical management of postpartum hemor-
rhage. If medical therapy fails, ligation of the uterine
or uteroovarian artery, infundibulopelvic vessels, or
hypogastric arteries, or hysterectomy may be indi-
cated.
H. Management of uterine inversion
1. The inverted uterus should be immediately reposi-
tioned vaginally. Blood and/or fluids should be
administered. If the placenta is still attached, it
should not be removed until the uterus has been
repositioned.
2. Uterine relaxation can be achieved with a
halogenated anesthetic agent. Terbutaline is also
useful for relaxing the uterus.
3. Following successful uterine repositioning and
placental separation, oxytocin (Pitocin) is given to
contract the uterus.
References: See page 208.

Postpartum Endometritis
Endometritis is an infection that begins in the decidua, and
then extends into the myometrium (endomyometritis) and
parametrium. Postpartum endometritis is a common cause
of postpartum fever, which is defined as an oral temperature
of >38.0 degrees Celsius (100.4 degrees Fahrenheit) on
any two of the first 10 days postpartum, exclusive of the first
24 hours. The first 24 hours are excluded because low
grade fever during this period is common and often resolves
spontaneously.

I. Microbiology. Postpartum endometritis is typically a

polymicrobial infection caused by two to three aerobes
and anaerobes from the genital tract.
A. Sexually transmitted infections, such as Neisseria
gonorrhoeae and Chlamydia trachomatis, are un-
common causes of postpartum endometritis, but
more frequent causes of endometritis unrelated to
pregnancy.
II. Risk factors. Cesarean delivery is the most important
risk factor for postpartum endometritis. The rates of
endometritis after nonelective cesarean, elective cesar-
ean, and vaginal delivery are about 30, 7, and <3%,
respectively.
A. Additional risk factors for postpartum endometritis
include:
1. Prolonged labor
2. Prolonged rupture of membranes
3. Multiple cervical examinations
4. Internal fetal or uterine monitoring
5. Large amount of meconium in amniotic fluid
6. Manual removal of the placenta
7. Low socioeconomic status
8. Maternal diabetes mellitus or severe anemia
9. Preterm birth
10. Bacterial vaginosis
11. Operative vaginal delivery
12. Postterm pregnancy
13. Colonization with group B streptococcus
B. Bacterial vaginosis is most important in the setting of
cesarean delivery. The odds of developing
postcesarean endometritis associated with bacterial
vaginosis are 5.8.
III. Clinical manifestations and diagnosis
A. Clinical findings. The diagnosis of postpartum
endometritis is largely based upon the findings of
fever and uterine tenderness occurring in a
postpartum woman. Other signs and symptoms
include foul lochia, chills, and lower abdominal pain.
The uterus may be soft and subinvoluted, which can
lead to excessive uterine bleeding. Sepsis is an un-
usual presentation.
B. Most cases develop within the first week after deliv-
ery, but 15% present between one and six weeks
 postpartum. Delayed presentation may manifest as
late postpartum hemorrhage.
C. Clostridium sordellii, streptococci, and staphylococci
can lead to endometritis with toxic shock syndrome.
D. Differential diagnosis of postpartum fever:
1. Surgical site infection (cesarean delivery incision,
episiotomy incision, perineal lacerations)
2. Mastitis or breast abscess
3. Urinary tract infection
4. Complications of anesthesia, such as aspiration
pneumonia.
5. Deep vein thrombosis and pulmonary embolism.
6. Disorders unrelated to pregnancy, such as appen-
dicitis and viral syndrome, should also be consid-
ered.
IV. Laboratory. An elevated white blood cell count sup-
ports the diagnosis, but can be a normal finding in
postpartum women. However, a rising neutrophil count
associated with elevated numbers of bands is sugges-
tive of an infectious process.
A. Cultures. Testing for gonorrhea and chlamydia
should be obtained if not previously performed, if
prior results were positive, or the patient is at high
risk for sexually transmitted infections. General
endometrial cultures are not performed routinely.
B. Bacteremia occurs in 10 to 20% of patients. Blood
cultures can be useful in guiding antimicrobial treat-
ment if the patient fails to respond to empiric therapy.
C. Imaging studies are used to search for other causes
of an initial postpartum fever (eg, pneumonia, deep
vein thrombosis, or pulmonary embolus) or persistent
postpartum fever (eg, abscess, ovarian vein throm-
bosis, septic pelvic thrombophlebitis) in patients
refractory to 48 to 72 hours of antimicrobial therapy.

Type and Frequency of Bacterial Isolates in

Postpartum Endometritis*

Isolate Frequency (percent)

Gram positive
Group B streptococci 8
Enterococci 7
S. epidermidis 9
Lactobacilli 4
Diphtheroids 2
S. Aureus 1

Gram negative
G. vaginalis 15
E. Coli 6
Enterobacterium spp. 2
P. mirabilis 2
Others 3

Anaerobic
S. bivius 11
Other Bacteroides spp. 9
Peptococci-peptostreptocci 22

Mycoplasma
U. urealyticum 39
M. hominis 11

C. trachomatis 2

V. Treatment
A. Broad spectrum parenteral antibiotics with coverage
for beta-lactamase producing anaerobes should be
initiated.
B. Clindamycin (900 mg every eight hours) plus
gentamicin (1.5 mg/kg every eight hours for patients
with normal renal function) is an effective regimen:
cure rates are 90 to 97%. Extended interval dosing
of gentamicin (5 mg/kg every 24 hours) is as effica-
cious as the thrice daily dosing.
C. Antibiotic regimens that are also effective include
cefotetan, cefoxitin, ceftizoxime, cefotaxime,
piperacillin with or without tazobactam, and
ampicillin/sulbactam.
D. Duration. Treatment should be continued until the
patient is clinically improved and afebrile for 24 to 48
hours. Oral antibiotics after parenteral treatment is
not required. However, if bacteremia was present,
oral antibiotic therapy should be continued to com-
plete a seven-day course.

Antibiotic Regimens for Endometritis

Clindamycin (900 mg IV Q 8 hours) plus gentamicin (1.5 mg/kg

IV Q 8 hours)
Ampicillin-sulbactam (Unasyn) 3 grams IV Q 6 hours
Ticarcillin-clavulanate (Timentin)3.1 grams IV Q 4 hours
Cefoxitin (Mefoxin) 2 grams IV Q 6 hours
Ceftriaxone (Rocephin) 2 grams IV Q 24 hours plus
metronidazole 500 mg PO or IV Q 8 hours*
Levofloxacin (Levaquin) 500 mg IV Q 24 hours plus
metronidazole 500 mg PO or IV Q 8 hours*

* Should not be given to breastfeeding mothers

If chlamydia infection is suspected, azithromycin 1 gram PO for
one dose should be added to the regimen

VI. Prevention
A. Antibiotic prophylaxis at cesarean delivery significantly
reduces the prevalence of postcesarean delivery
endometritis, for both elective and nonelective proce-
dures. A single dose of cefazolin (Ancef) 2 g IV or
ampicillin is given just after cord clamping.
References: See page 208.

Postpartum Fever Workup

History: Postpartum fever is >100.4 F (38 degrees C) on 2
occasions >6h apart after the first postpartum day (during
the first 10 days postpartum), or >101 on the first
postpartum day. Dysuria, abdominal pain, distention, breast
pain, calf pain.
Predisposing Factors: Cesarean section, prolonged labor,
premature rupture of membranes, internal monitors, multi-
ple vaginal exams, meconium, manual placenta extraction,
anemia, poor nutrition.
Physical Examination: Temperature, throat, chest, lung
exams; breasts, abdomen. Costovertebral angle tender-
ness, uterine tenderness, phlebitis, calf tenderness; wound
exam. Speculum exam.
Differential Diagnosis: UTI, upper respiratory infection,
atelectasis, pneumonia, wound infection, mastitis,
episiotomy abscess; uterine infection, deep vein thrombo-
sis, pyelonephritis, pelvic abscess.
Labs: CBC, SMA7, blood C&S x 2, catheter UA, C&S.
Gonococcus culture, chlamydia; wound C&S, CXR.

References

References may be obtained at www.ccspublishing.com/ccs